1: J Endocrinol. 1999 Nov;163(2):207-12. Related Articles, Links Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. Persaud SJ, Al-Majed H, Raman A, Jones PM. Physiology Division, School of Biomedical Sciences, King's College, London, UK. To determine whether extracts of Gymnema sylvestre may have therapeutic potential for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), we examined the effects of an alcoholic extract of G. sylvestre (GS4) on insulin secretion from rat islets of Langerhans and several pancreatic beta-cell lines. GS4 stimulated insulin release from HIT-T15, MIN6 and RINm5F beta-cells and from islets in the absence of any other stimulus, and GS4-stimulated insulin secretion was inhibited in the presence of 1 mM EGTA. Blockade of voltage-operated Ca(2+) channels with 10 microM isradipine did not significantly affect GS4-induced secretion, and insulin release in response to GS4 was independent of incubation temperature. Examination of islet and beta-cell integrity after exposure to GS4, by trypan blue exclusion, indicated that concentrations of GS4 that stimulated insulin secretion also caused increased uptake of dye. Two gymnemic acid-enriched fractions of GS4, obtained by size exclusion and silica gel chromatography, also caused increases in insulin secretion concomitant with increased trypan blue uptake. These results confirm the stimulatory effects of G. sylvestre on insulin release, but indicate that GS4 acts by increasing cell permeability, rather than by stimulating exocytosis by regulated pathways. Thus the suitability of GS4 as a potential novel treatment for NIDDM can not be assessed by direct measurements of beta-cell function in vitro. PMID: 10556769 [PubMed - indexed for MEDLINE] Am J Physiol. 1998 May;274(5 Pt 2):R1324-30. Related Articles, Links Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the diabetic db/db mouse. Ninomiya Y, Imoto T, Yatabe A, Kawamura S, Nakashima K, Katsukawa H. Department of Oral Physiology, Chemistry and Pediatric Dentistry, Asahi University School of Dentistry, Gifu, Japan. Genetically diabetic db/db mice show greater neural and behavioral responses to sugars than lean control mice. The present study examined chorda tympani responses of db/db mice to nonsugar sweeteners and their inhibition by a sweet response inhibitor, gurmarin. The results showed that responses to sucrose, saccharin, glycine, L-alanine, and D-tryptophan, but not to D-phenylalanine, were approximately 1.5 times greater in db/db mice than in control mice. Treatment of the tongue with gurmarin suppressed responses to these sweeteners in db/db and control mice, but the extent of suppression was considerably smaller in db/db mice. The magnitudes of gurmarin-sensitive components of the response to sweeteners in db/db mice were not significantly different from those in control mice, whereas the magnitudes of gurmarin-insensitive components in db/db mice were about twice as large as those in control mice. These results suggest that the enhancement of chorda tympani responses in db/db mice to sucrose and other nonsugar sweeteners may occur through gurmarin-insensitive membrane components. PMID: 9644046 [PubMed - indexed for MEDLINE] J Ethnopharmacol. 1990 Oct;30(3):295-300. Related Articles, Links Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER. Department of Biochemistry, Postgraduate Institute of Basic Medical Sciences Madras, India. The effectiveness of GS4, an extract from the leaves of Gymnema sylvestre, in controlling hyperglycaemia was investigated in 22 Type 2 diabetic patients on conventional oral antihyperglycaemic agents. GS4 (400 mg/day) was administered for 18-20 months as a supplement to the conventional oral drugs. During GS4 supplementation, the patients showed a significant reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins, and conventional drug dosage could be decreased. Five of the 22 diabetic patients were able to discontinue their conventional drug and maintain their blood glucose homeostasis with GS4 alone. These data suggest that the beta cells may be regenerated/repaired in Type 2 diabetic patients on GS4 supplementation. This is supported by the appearance of raised insulin levels in the serum of patients after GS4 supplementation. Keywords for above are: gymnema sylvestre, niddm J Ethnopharmacol. 1990 Oct;30(3):265-79. Related Articles, Links Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. Shanmugasundaram ER, Gopinath KL, Radha Shanmugasundaram K, Rajendran VM. Department of Biochemistry, University of Madras, India. Two water soluble extracts, GS3 and GS4, obtained from the leaves of Gymnema sylvestre, were tested in streptozotocin treated rats for their effects on blood glucose homeostasis and pancreatic endocrine tissue. In the diabetic rats, fasting blood glucose levels returned to normal after 60 days of GS3 and after 20 days of GS4 oral administration. Blood collected during the conduct of oral glucose tolerance tests was used to assay for serum insulin. GS3 and GS4 therapy led to a rise in serum insulin to levels closer to normal fasting levels. In diabetic rat pancreas, both GS3 and GS4 were able to double the islet number and beta cell number. This herbal therapy appears to bring about blood glucose homeostasis through increased serum insulin levels provided by repair/regeneration of the endocrine pancreas. PMID: 2259215 [PubMed - indexed for MEDLINE] Diabetes Res Clin Pract. 1990 May-Jun;9(2):143-8. Related Articles, Links Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats. Okabayashi Y, Tani S, Fujisawa T, Koide M, Hasegawa H, Nakamura T, Fujii M, Otsuki M. Second Department of Internal Medicine, Kobe University School of Medicine, Japan. Effect of Gymnema sylvestre, R.Br. (G. sylvestre; GS4) on glucose homeostasis was studied in rats. In the first set of experiments, the acute effect of GS4 was examined in both non-diabetic and streptozocin (30 mg/kg)-induced mildly diabetic rats. Administration of 1 g/kg body weight of GS4 to 18-h fasted non-diabetic rats significantly attenuated the serum glucose response to oral administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in GS4-administered rats was lower, but not significantly, than that in control rats. In mildly diabetic rats, a 60 min increment in serum glucose concentrations was significantly reduced by GS4 administration. No IRI response was observed in these diabetic rats irrespective of GS4 administration. In the second set of experiments, the chronic effect of GS4 was examined in mildly diabetic rats. Two weeks after the induction of diabetes, the rats were divided into two groups that had similar impairment of glucose tolerance assessed by an oral glucose loading test. The rats were fed for 32-35 days with either a control diet or a diet supplemented with GS4. After 4 weeks, GS4 showed a tendency to reduce the serum glucose concentrations in the fed state and to improve the glucose tolerance. Gain in body weight, food intake, pancreas weight and the pancreatic contents of IRI, protein, amylase and trypsinogen were unaltered in the GS4-treated group compared with the control. These results suggest the usefulness of G. sylvestre in the treatment of certain classes of noninsulin-dependent diabetes mellitus. PMID: 1695875 [PubMed - indexed for MEDLINE] Pancreas. 1991 Mar;6(2):221-8. Related Articles, Links Effects of leucine on insulin secretion and beta cell membrane potential in mouse islets of Langerhans. Brouwer AE, Carroll PB, Atwater IJ. University of Leiden, Faculty of Medicine, The Netherlands. Leucine is known to enhance insulin secretion from islets of Langerhans, and insulin promotes leucine uptake in peripheral tissues. The present studies were designed to elucidate the effects of leucine on glucose responsiveness and stimulus secretion coupling in mouse islets of Langerhans. The effects of 20 mM leucine on insulin secretion and membrane potential were studied over a range of glucose concentrations (0-27.7 mM). Microdissected, perifused pancreatic islets from normal adult mice were used for both studies of insulin secretion and electrophysiology in order to make a close comparison between these measurements. Leucine enhanced the insulin secretion in the presence of 5.6, 11.1, and 22.2 mM glucose. In the presence of leucine, 27 mM glucose inhibited insulin secretion. In the absence of glucose-leucine did not induce electrical activity of the beta cell membrane, whereas in the presence of 5.6, 11.1, and 22.2 mM glucose leucine increased spike frequency. Thus, leucine shifts both the glucose-dependent insulin secretion and electrical activity toward lower glucose concentrations. It is concluded that leucine and glucose share a common metabolic pathway (citric acid cycle) for stimulatory effects. Leucine is deaminated to form 2-ketoisocaproic acid (KIC) and produce NH4+. We propose that in the absence of glucose this increases cytosolic pH, which in turn increases K+ permeability, and inhibits electrical activity and insulin secretion. PMID: 1886890 [PubMed - indexed for MEDLINE] J Endocrinol. 1989 Jun;121(3):479-85. Related Articles, Links Effects of islet hormones on insulin secretion from cloned B cell lines, HIT-T15 and RINm5F. Lambert DG, Atkins TW. Pharmaceutical Sciences Institute, Aston University, Birmingham. The effects of the islet cell hormones glucagon, somatostatin-28 and pancreatic polypeptide on insulin secretion from cultured cloned pancreatic B cells (HIT-T15 and RINm5F) have been investigated. Glucagon stimulates the secretion of insulin from HIT-T15 cells in the absence and presence of glucose and from RINm5F cells in the absence and presence of glyceraldehyde. HITT15 cells were more sensitive to the stimulatory effect of glucagon than RINm5F cells. Somatostatin-28 and pancreatic polypeptide, both alone and in combination, reduced glucose- and glucagon-stimulated insulin release from HIT-T15 cells and glyceraldehyde- and glucagonstimulated insulin release from RINm5F cells. HIT-T15 cells were more sensitive to the inhibitory actions of somatostatin-28 and pancreatic polypeptide than RINm5F cells. This study supports the hypothesis that insulin release from normal B cells may be modified by the paracrine activity of islet hormones, glucagon, somatostatin and pancreatic polypeptide and probably occurs before any fine tuning imposed by subsequently released insulin. PMID: 2569024 [PubMed - indexed for MEDLINE] Proc Natl Acad Sci U S A. 1984 Mar;81(6):1822-6. Related Articles, Links Bombesin stimulates insulin secretion by a pancreatic islet cell line. Swope SL, Schonbrunn A. The amphibian tetradecapeptide, bombesin (BBS) has been shown to stimulate insulin secretion both in vivo and by pancreatic islet cells in vitro. To determine whether BBS can act directly on pancreatic beta cells, we examined its effects on insulin secretion by HIT-T15 cells (HIT cells), a clonal islet cell line. Addition of 100 nM BBS to HIT cells stimulated insulin release 25-fold within 30 sec. The rapid stimulatory effect of BBS on insulin release was short-lived: the secretory rate returned to basal levels after 90 min of BBS treatment. The decrease in the rate of insulin release in the continued presence of BBS was due not to depletion of intracellular insulin stores but to specific desensitization to this peptide. Stimulation of insulin secretion by BBS was dose dependent with an ED50 value (0.51 +/- 0.15 nM) similar to the concentration of BBS-like immunoreactive material in rat plasma. Five BBS analogs, including porcine gastrin-releasing peptide, were as powerful as BBS in stimulating insulin release. The relative potencies of the analogs tested indicated that the COOH-terminal octapeptide sequence in BBS was sufficient for stimulation of release. In contrast, 14 peptides structurally unrelated to BBS did not alter insulin secretion. BBS action was synergistic with that of glucagon; insulin secretion in the presence of maximal concentrations of both peptides was greater than the additive effects of the two peptides added individually. Somatostatin inhibited BBS-stimulated release by 69 +/- 1% with an ID50 value of 3.2 +/- 0.3 nM. These results show that BBS stimulation of insulin secretion by a clonal pancreatic cell line closely parallels its effects in vivo and support the hypothesis that BBS stimulates insulin secretion by a direct effect on the pancreatic beta cell. The clonal HIT cell line provides a homogeneous cell preparation amenable for studies on the biochemical mechanisms of BBS action in the endocrine pancreas. PMID: 6143320 [PubMed - indexed for MEDLINE] 1: J Endocrinol. 1999 Nov;163(2):207-12. Related Articles, Links Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. Persaud SJ, Al-Majed H, Raman A, Jones PM. Physiology Division, School of Biomedical Sciences, King's College, London, UK. To determine whether extracts of Gymnema sylvestre may have therapeutic potential for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), we examined the effects of an alcoholic extract of G. sylvestre (GS4) on insulin secretion from rat islets of Langerhans and several pancreatic beta-cell lines. GS4 stimulated insulin release from HIT-T15, MIN6 and RINm5F beta-cells and from islets in the absence of any other stimulus, and GS4-stimulated insulin secretion was inhibited in the presence of 1 mM EGTA. Blockade of voltage-operated Ca(2+) channels with 10 microM isradipine did not significantly affect GS4-induced secretion, and insulin release in response to GS4 was independent of incubation temperature. Examination of islet and beta-cell integrity after exposure to GS4, by trypan blue exclusion, indicated that concentrations of GS4 that stimulated insulin secretion also caused increased uptake of dye. Two gymnemic acid-enriched fractions of GS4, obtained by size exclusion and silica gel chromatography, also caused increases in insulin secretion concomitant with increased trypan blue uptake. These results confirm the stimulatory effects of G. sylvestre on insulin release, but indicate that GS4 acts by increasing cell permeability, rather than by stimulating exocytosis by regulated pathways. Thus the suitability of GS4 as a potential novel treatment for NIDDM can not be assessed by direct measurements of beta-cell function in vitro. PMID: 10556769 [PubMed - indexed for MEDLINE] 2: Am J Physiol. 1998 May;274(5 Pt 2):R1324-30. Related Articles, Links Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the diabetic db/db mouse. Ninomiya Y, Imoto T, Yatabe A, Kawamura S, Nakashima K, Katsukawa H. Department of Oral Physiology, Chemistry and Pediatric Dentistry, Asahi University School of Dentistry, Gifu, Japan. Genetically diabetic db/db mice show greater neural and behavioral responses to sugars than lean control mice. The present study examined chorda tympani responses of db/db mice to nonsugar sweeteners and their inhibition by a sweet response inhibitor, gurmarin. The results showed that responses to sucrose, saccharin, glycine, L-alanine, and D-tryptophan, but not to D-phenylalanine, were approximately 1.5 times greater in db/db mice than in control mice. Treatment of the tongue with gurmarin suppressed responses to these sweeteners in db/db and control mice, but the extent of suppression was considerably smaller in db/db mice. The magnitudes of gurmarin-sensitive components of the response to sweeteners in db/db mice were not significantly different from those in control mice, whereas the magnitudes of gurmarin-insensitive components in db/db mice were about twice as large as those in control mice. These results suggest that the enhancement of chorda tympani responses in db/db mice to sucrose and other nonsugar sweeteners may occur through gurmarin-insensitive membrane components. PMID: 9644046 [PubMed - indexed for MEDLINE] 3: J Ethnopharmacol. 1990 Oct;30(3):295-300. Related Articles, Links Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER. Department of Biochemistry, Postgraduate Institute of Basic Medical Sciences Madras, India. The effectiveness of GS4, an extract from the leaves of Gymnema sylvestre, in controlling hyperglycaemia was investigated in 22 Type 2 diabetic patients on conventional oral antihyperglycaemic agents. GS4 (400 mg/day) was administered for 18-20 months as a supplement to the conventional oral drugs. During GS4 supplementation, the patients showed a significant reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins, and conventional drug dosage could be decreased. Five of the 22 diabetic patients were able to discontinue their conventional drug and maintain their blood glucose homeostasis with GS4 alone. These data suggest that the beta cells may be regenerated/repaired in Type 2 diabetic patients on GS4 supplementation. This is supported by the appearance of raised insulin levels in the serum of patients after GS4 supplementation. Publication Types: Clinical Trial PMID: 2259217 [PubMed - indexed for MEDLINE] 4: J Ethnopharmacol. 1990 Oct;30(3):265-79. Related Articles, Links Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. Shanmugasundaram ER, Gopinath KL, Radha Shanmugasundaram K, Rajendran VM. Department of Biochemistry, University of Madras, India. Two water soluble extracts, GS3 and GS4, obtained from the leaves of Gymnema sylvestre, were tested in streptozotocin treated rats for their effects on blood glucose homeostasis and pancreatic endocrine tissue. In the diabetic rats, fasting blood glucose levels returned to normal after 60 days of GS3 and after 20 days of GS4 oral administration. Blood collected during the conduct of oral glucose tolerance tests was used to assay for serum insulin. GS3 and GS4 therapy led to a rise in serum insulin to levels closer to normal fasting levels. In diabetic rat pancreas, both GS3 and GS4 were able to double the islet number and beta cell number. This herbal therapy appears to bring about blood glucose homeostasis through increased serum insulin levels provided by repair/regeneration of the endocrine pancreas. PMID: 2259215 [PubMed - indexed for MEDLINE] 5: Diabetes Res Clin Pract. 1990 May-Jun;9(2):143-8. Related Articles, Links Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats. Okabayashi Y, Tani S, Fujisawa T, Koide M, Hasegawa H, Nakamura T, Fujii M, Otsuki M. Second Department of Internal Medicine, Kobe University School of Medicine, Japan. Effect of Gymnema sylvestre, R.Br. (G. sylvestre; GS4) on glucose homeostasis was studied in rats. In the first set of experiments, the acute effect of GS4 was examined in both non-diabetic and streptozocin (30 mg/kg)-induced mildly diabetic rats. Administration of 1 g/kg body weight of GS4 to 18-h fasted non-diabetic rats significantly attenuated the serum glucose response to oral administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in GS4-administered rats was lower, but not significantly, than that in control rats. In mildly diabetic rats, a 60 min increment in serum glucose concentrations was significantly reduced by GS4 administration. No IRI response was observed in these diabetic rats irrespective of GS4 administration. In the second set of experiments, the chronic effect of GS4 was examined in mildly diabetic rats. Two weeks after the induction of diabetes, the rats were divided into two groups that had similar impairment of glucose tolerance assessed by an oral glucose loading test. The rats were fed for 32-35 days with either a control diet or a diet supplemented with GS4. After 4 weeks, GS4 showed a tendency to reduce the serum glucose concentrations in the fed state and to improve the glucose tolerance. Gain in body weight, food intake, pancreas weight and the pancreatic contents of IRI, protein, amylase and trypsinogen were unaltered in the GS4-treated group compared with the control. These results suggest the usefulness of G. sylvestre in the treatment of certain classes of noninsulin-dependent diabetes mellitus. PMID: 1695875 [PubMed - indexed for MEDLINE] 6: Phytomedicine. 2002 May;9(4):346-51. Related Articles, Links Extract of Ocimum canum lowers blood glucose and facilitates insulin release by isolated pancreatic beta-islet cells. Nyarko AK, Asare-Anane H, Ofosuhene M, Addy ME. Noguchi Memorial Institute for Medical Research, University of Ghana, Legon. anyarko@noguchi.mimcom.net Aqueous extract of Ocimum canum Sim, (Lamiaceae) is used by some Ghanaians to manage diabetes mellitus. In vivo modulation of levels of fasting blood glucose by 0. canum extract was evaluated in type-II diabetes mellitus using the C57BL/KsJ db/db genetically diabetic animal model, and its effects on glucose-stimulated insulin release in vitro were monitored using isolated rat pancreatic beta-islet cells. The results showed that fasting blood glucose levels and body weight decreased significantly (p < 0.05) in diabetic and non-diabetic C57BL/KsJ mice, which were administered aqueous extract of 0. canum. In vitro, the 0. canum extract significantly enhanced insulin release from isolated rat pancreatic beta-islet cells. Insulin release was found to be dependent on glucose concentration and increased with increasing O. canum concentration in the incubation medium up to an optimum extract concentration of 0.03 mg/ml. Release of the hormone decreased beyond this concentration of extract in the medium. Addition to the medium of Desmodium adscendens, a plant preparation used to manage inflammatory disorders, did not increase but rather inhibited insulin secretion by the pancreatic beta-islet cells. These results could explain the use of 0. canum in Ghanaian folk medicine to manage diabetes mellitus. PMID: 12120816 [PubMed - indexed for MEDLINE] 7: Diabetes. 2003 Feb;52(2):356-64. Related Articles, Links Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known. Straub SG, Mulvaney-Musa J, Yajima H, Weiland GA, Sharp GW. Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. Denatonium, one of the most bitter-tasting substances known, stimulated insulin secretion in clonal HIT-T15 beta-cells and rat pancreatic islets. Stimulation of release began promptly after exposure of the beta-cells to denatonium, reached peak rates after 4-5 min, and then declined to near basal values after 20-30 min. In islets, no effect was observed at 2.8 mmol/;l glucose, whereas a marked stimulation was observed at 8.3 mmol/;l glucose. No stimulation occurred in the absence of extracellular Ca(2+) or in the presence of the Ca(2+)-channel blocker nitrendipine. Stimulated release was inhibited by alpha(2)-adrenergic agonists. Denatonium had no direct effect on voltagegated calcium channels or on cyclic AMP levels. There was no evidence for the activation of gustducin or transducin in the beta-cell. The results indicate that denatonium stimulates insulin secretion by decreasing KATP channel activity, depolarizing the beta-cell, and increasing Ca(2+) influx. Denatonium did not displace glybenclamide from its binding sites on the sulfonylurea receptor (SUR). Strikingly, it increased glybenclamide binding by decreasing the K(d). It is concluded that denatonium, which interacts with K(+) channels in taste cells, most likely binds to and blocks Kir6.2. A consequence of this is a conformational change in SUR to increase the SUR/glybenclamide binding affinity. PMID: 12540608 [PubMed - indexed for MEDLINE] 8: Diabetologia. 1989 Jun;32(6):354-9. Related Articles, Links The hypoglycaemic and insulinotropic activity of Tinospora crispa: studies with human and rat islets and HIT-T15 B cells. Noor H, Hammonds P, Sutton R, Ashcroft SJ. Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Headington, Oxford, UK. In Malaysia, Tinospora crispa extract is taken orally by Type 2 (non-insulin-dependent) diabetic patients to treat hyperglycaemia. We have evaluated the claimed hypoglycaemic property by adding aqueous extract to the drinking water of normal and alloxan-diabetic rats. After one week, fasting blood glucose levels were significantly (p less than 0.01) lower and serum insulin levels were significantly (p less than 0.01) higher in treated diabetic animals (10.4 +/- 1.0 mmol/l and 12.8 +/- 1.1 muU/ml respectively) compared to untreated diabetic controls (17.4 +/- 1.7 mmol/l and 8.0 +/- 0.7 muU/ml respectively). The insulinotropic action of T. crispa was further investigated in vitro using isolated human or rat islets of Langerhans and HIT-T15 cells. In static incubations with rat islets and HIT-T15 B cells, the extract induced a dosage dependent stimulation and potentiation of basal and glucose-stimulated insulin secretion respectively. This insulinotropic effect was also evident in perifused human and rat islets and HIT-T5 B-cells. The observations that (i) in all three models insulin secretory rates rapidly returned to basal levels on removal of the extract and (ii) in rat islets, a second challenge with T. crispa induced an additional, stimulated response, are all consistent with physiological release of insulin by B cells. Moreover, the rate of HIT-T15 glucose utilisation was not affected by incubation with T. crispa, suggesting that the cells were viable throughout. These are the first studies to provide biochemical evidence which substantiates the traditional claims for an oral hypoglycaemic effect of Tinospora crispa, and which also show that the hypoglycaemic effect is associated with increased insulin secretion. PMID: 2668082 [PubMed - indexed for MEDLINE] 9: J Ethnopharmacol. 2002 Aug;81(3):317-20. Related Articles, Links Glucose lowering effect of aqueous extract of Enicostemma littorale Blume in diabetes: a possible mechanism of action. Maroo J, Vasu VT, Aalinkeel R, Gupta S. Department of Biochemistry, Faculty of Science, M. S. University, Baroda Gujarat 390 002, India. Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. Enicostemma littorale Blume is a small herb and recently we have reported its blood glucose lowering potential in alloxan induced diabetic rats. A single dose of aqueous extract of E. littorale (15 g dry plant equivalent extract per kg) had shown significant increase in the serum insulin levels in alloxaninduced diabetic rats at 8 h. The insulinotropic action of aqueous extract of E. littorale was further investigated using rat pancreatic islets. Extract has the potential to enhance glucose-induced insulin release at 11.1 mM glucose from isolated rat pancreatic islets and was partially able to reverse the effect of diazoxide (0.25 mM). Incubation with Ca(2+) chelator (EGTA) and Ca(2+) channel blocker (nimodipine) did not affect the glucose-induced insulin release augmented by the extract. Above results suggest the glucose lowering effect of aqueous extract of E. littorale to be associated with potentiation of glucose-induced insulin release through K(+)-ATP channel dependent pathway but did not require Ca(2+) influx. PMID: 12127231 [PubMed - indexed for MEDLINE] 10: J Nutr. 1992 Dec;122(12):2367-73. Related Articles, Links An extract of Gymnema sylvestre leaves and purified gymnemic acid inhibits glucosestimulated gastric inhibitory peptide secretion in rats. Fushiki T, Kojima A, Imoto T, Inoue K, Sugimoto E. Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Japan. Gastric inhibitory peptide release into the portal vein in response to duodenal infusion of Dglucose was studied in the presence of a leaf extract of Gymnema sylvestre, purified gymnemic acid and inhibitors of some putative glucose sensors and carriers in the intestinal lumen. Intraduodenal infusion of D-glucose significantly increased the portal immunoreactive gastric inhibitory peptide concentration in a dose-dependent manner. The increase in the portal immunoreactive gastric inhibitory peptide induced by glucose was significantly depressed by concomitantly infused leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin but not by cytochalasin B. Mannoheptulose, which inhibits glycolysis, and procaine and lidocaine, which inhibit the vagal glucoreceptor in the lumen, did not affect portal immunoreactive gastric inhibitory peptide concentrations. These results suggest that a glucose receptor, which interacts with the leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin, exists for the release of immunoreactive gastric inhibitory peptide and that the glucose receptor for gastric inhibitory peptide release is not likely to be identical with a glucose transporter or a vagal glucoreceptor in the lumen. PMID: 1453221 [PubMed - indexed for MEDLINE] 11: Diabetes. 2002 Dec;51(12):3450-60. Related Articles, Links Exogenous nitric oxide and endogenous glucose-stimulated beta-cell nitric oxide augment insulin release. Smukler SR, Tang L, Wheeler MB, Salapatek AM. Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. The role nitric oxide (NO) plays in physiological insulin secretion has been controversial. Here we present evidence that exogenous NO stimulates insulin secretion, and that endogenous NO production occurs and is involved in the regulation of insulin release. Radioimmunoassay measurement of insulin release and a dynamic assay of exocytosis using the dye FM1-43 demonstrated that three different NO donors-hydroxylamine (HA), sodium nitroprusside, and 3morpholinosydnonimine (SIN-1)-each stimulated a marked increase in insulin secretion from INS1 cells. Pharmacological manipulation of the guanylate cyclase/guanosine 3',5'-cyclic monophosphate pathway indicated that this pathway was involved in mediating the effect of the intracellular NO donor, HA, which was used to simulate endogenous NO production. This effect was further characterized as involving membrane depolarization and intracellular Ca(2+) ([Ca(2+)](i)) elevation. SIN-1 application enhanced glucose-induced [Ca(2+)](i) responses in primary beta-cells and augmented insulin release from islets in a glucose-dependent manner. Realtime monitoring of NO using the NO-sensitive fluorescent dye, diaminofluorescein, was used to provide direct and dynamic imaging of NO generation within living beta-cells. This showed that endogenous NO production could be stimulated by elevation of [Ca(2+)](i) levels and by glucose in both INS-1 and primary rat beta-cells. Scavenging endogenously produced NO-attenuated glucose-stimulated insulin release from INS-1 cells and rat islets. Thus, the results indicated that applied NO is able to exert an insulinotropic effect, and implicated endogenously produced NO in the physiological regulation of insulin release. PMID: 12453899 [PubMed - indexed for MEDLINE] 12: J Biol Chem. 1994 Jan 14;269(2):1041-5. Related Articles, Links Ascorbic acid and insulin secretion in pancreatic islets. Bergsten P, Moura AS, Atwater I, Levine M. Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. The effect of ascorbic acid on glucose-induced insulin release from single pancreatic islets was measured using a new, ultra-sensitive enzyme-linked immunosorbent insulin assay. Within 20 s ascorbic acid inhibited insulin secretion; inhibition was dose dependent and completely reversible. There was a 50% inhibition of the secretory response with 200 microM ascorbic acid and 90% inhibition with 400 microM ascorbic acid. The decrease in insulin secretion was recorded as a reduction of the amplitudes of the fast insulin transients, which give rise to the oscillatory nature of insulin secretion. The inhibition of glucose-induced insulin release by ascorbic acid was associated with hyperpolarization of the pancreatic beta-cell. Suppression of glucose-induced membrane depolarization was evident after 20 s, was dose dependent, and was completely reversible. The data here may provide the first explanation of why plasma ascorbate concentrations are tightly controlled. PMID: 8288558 [PubMed - indexed for MEDLINE] 13: Pancreas. 1997 Jul;15(1):69-77. Related Articles, Links Vitamin A stimulation of insulin secretion: effects on transglutaminase mRNA and activity using rat islets and insulin-secreting cells. Driscoll HK, Adkins CD, Chertow TE, Cordle MB, Matthews KA, Chertow BS. Medical Service, VA Medical Center, Huntington, West Virginia, USA. Retinol or retinoic acid is required for insulin release. Retinoids increase transglutaminase activity, and transglutaminase has been implicated in islet insulin release. To examine whether transglutaminase could mediate effects of retinoids on insulin secretion, we measured (i) transglutaminase activity in islets from rats deficient in vitamin A or repleted with retinol or retinoic acid, (ii) transglutaminase activity in RINm5F and INS-1 insulin-secreting cells cultured in retinol or retinoic acid, (iii) mRNA for transglutaminase in RINm5F and INS-1 cells, and (iv) insulin secretion from INS-1 cells in response to retinoic acid. Islets from rats repleted with retinol or retinoic acid showed more than twice the transglutaminase activity of islets from vitamin A deficient rats. Retinoic acid increased RINm5F cells and INS-1 cell transglutaminase activity. Retinol did not increase transglutaminase activity. Transglutaminase mRNA was detected in INS1 cells but not in RINm5F cells. Retinoic acid increased insulin secretion from INS-1 cells as observed previously in RINm5F cells. In conclusion, retinoic acid increases transglutaminase activity in both rat islets and two insulin-secreting from INS-1 cells. Transglutaminase is a candidate for mediating retinoid-induced changes in insulin secretion. PMID: 9211495 [PubMed - indexed for MEDLINE] 14: Acta Biol Med Ger. 1982;41(12):1229-40. Related Articles, Links The insulin-releasing activity of the tropical plant momordica charantia. Welihinda J, Arvidson G, Gylfe E, Hellman B, Karlsson E. An aqueous extract from the unripe fruits of the tropical plant Momordica charantia was found to be a potent stimulator of insulin release from beta-cell-rich pancreatic islets isolated from obesehyperglycemic mice. The stimulation of insulin release was partially reversible. It differed from that of D-glucose and other commonly employed insulin secretagogues in not being suppressed by L-epinephrine and in even being potentiated by the removal of Ca2+. This anomalous behaviour was not associated with general effects on the metabolism of the beta-cells as indicated by an unaltered oxidation of D-glucose. Studies of 45Ca fluxes suggest that the insulin-releasing action is the result of perturbations of membrane functions. In support for the idea of direct effects on membrane lipids, the action of the extract was found to mimic that of saponin in inhibiting the Ca2+/H+ exchange mediated by the ionophore A23187 in isolated chromaffin granules and release Ca2+ from preloaded liposomes. PMID: 6765165 [PubMed - indexed for MEDLINE] 15: Am J Physiol Endocrinol Metab. 2001 Nov;281(5):E1082-7. Related Articles, Links Chronic exposure to high leucine impairs glucose-induced insulin release by lowering the ATP-to-ADP ratio. Anello M, Ucciardello V, Piro S, Patane G, Frittitta L, Calabrese V, Giuffrida Stella AM, Vigneri R, Purrello F, Rabuazzo AM. Institute of Internal Medicine, Endocrinology, and Metabolism and S. Signorelli Diabetes Center, Ospedale Garibaldi, Italy. segmeint@mbox.unict.it Exposure of rat pancreatic islets to 20 mM leucine for 24 h reduced insulin release in response to glucose (16.7 and 22.2 mM). Insulin release was normal when the same islets were stimulated with leucine (40 mM) or glyburide (1 microM). To investigate the mechanisms responsible for the different effect of these secretagogues, we studied several steps of glucose-induced insulin secretion. Glucose utilization and oxidation rates in leucine-precultured islets were similar to those of control islets. Also, the ATP-sensitive K(+) channel-independent pathway of glucosestimulated insulin release, studied in the presence of 30 mM K(+) and 250 microM diazoxide, was normal. In contrast, the ATP-to-ADP ratio after stimulation with 22.2 mM glucose was reduced in leucine-exposed islets with respect to control islets. The decrease of the ATP-to-ADP ratio was due to an increase of ADP levels. In conclusion, prolonged exposure of pancreatic islets to high leucine levels selectively impairs glucose-induced insulin release. This secretory abnormality is associated with (and might be due to) a reduced ATP-to-ADP ratio. The abnormal plasma amino acid levels often present in obesity and diabetes may, therefore, affect pancreatic islet insulin secretion in these patients. PMID: 11595666 [PubMed - indexed for MEDLINE] 16: Planta Med. 2000 Jun;66(5):418-23. Related Articles, Links Insulinotropic effect of Citrullus colocynthis fruit extracts. Nmila R, Gross R, Rchid H, Roye M, Manteghetti M, Petit P, Tijane M, Ribes G, Sauvaire Y. Laboratoire de Recherche sur les Substances Naturelles Vegetales (UPRES EA 1677), Universite Montpellier II, France. Infusions of Citrullus colocynthis Schrad. (Cucurbitaceae) fruits are traditionally used as antidiabetic medication in Mediterranean countries, but to our knowledge no studies have been undertaken so far to determine the possible mechanisms involved in the antidiabetic properties of the fruit. The present study was designed to investigate whether these fruits possess insulinotropic effects. For this purpose, different extracts of Citrullus colocynthis seed components were obtained: RN II (crude extract), RN VI (hydro-alcoholic extract), RN X (purified extract) and RN XVII (beta-pyrazol-1-ylalanine), the major free amino acid present in the seeds. The insulin secretory effects of these different extracts were evaluated in vitro in the isolated rat pancreas and isolated rat islets in the presence of 8.3 mM glucose. All tested extracts, when perfused for 20 min at 0.1 mg/ml, immediately and significantly stimulated insulin secretion. This effect was transient. In addition, the purified extract (RN X) provoked a clear dose-dependent increase in insulin release from isolated islets. Moreover, a significant and persistant increase in pancreatic flow rate appeared during RN VI, RN X and RN XVII perfusions. In conclusion, our results show that different Citrullus colocynthis seed extracts have an insulinotropic effect which could at least partially account for the antidiabetic activities of these fruits. PMID: 10909260 [PubMed - indexed for MEDLINE] 17: Obes Res. 2000 Sep;8(6):475-80. Related Articles, Links Augmented insulinotropic action of arachidonic acid through the lipoxygenase pathway in the obese Zucker rat. Ahren B, Magrum LJ, Havel PJ, Greene SF, Phinney SD, Johnson PR, Stern JS. Department of Medicine, Lund University, Malmo, Sweden. bo.ahren@medforsk.mas.lu.se OBJECTIVE: The metabolism of arachidonic acid (AA) has been shown to be altered in severe insulin resistance that is present in obese (fa/fa) Zucker rats. We examined the effects and mechanism of action of AA on basal and glucose-stimulated insulin secretion in pancreatic islets isolated from obese (fa/fa) Zucker rats and their homozygous lean (Fa/Fa) littermates. RESEARCH METHODS AND PROCEDURES: Islets were isolated from 10- to 12-week-old rats and incubated for 45 minutes in glucose concentrations ranging from 3.3 to 16.7 mM with or without inhibitors of the cyclooxygenase or lipoxygenase pathways. Medium insulin concentrations were measured by radioimmunoassay, and islet production of the 12-lipoxygenase metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), was measured by enzyme immunoassay. RESULTS: In islets from lean animals, AA stimulated insulin secretion at submaximally stimulatory glucose levels (<11.1 mM) but not at 16.7 mM glucose. In contrast, in islets derived from obese rats, AA potentiated insulin secretion at all glucose concentrations. AA-induced insulin secretion was augmented in islets from obese compared with lean rats at high concentrations of AA in the presence of 3.3 mM glucose. Furthermore, the inhibitor of 12lipoxygenase, esculetin (0.5 microM), inhibited AA-stimulated insulin secretion in islets from obese but not lean rats. Finally, the islet production of the 12-HETE was markedly enhanced in islets from obese rats, both in response to 16.7 mM glucose and to AA. DISCUSSION: The insulin secretory response to AA is augmented in islets from obese Zucker rats by a mechanism related to enhanced activity of the 12-lipoxygenase pathway. Therefore, augmented action of AA may be a mechanism underlying the adaptation of insulin secretion to the increased demand caused by insulin resistance in these animals. PMID: 11011915 [PubMed - indexed for MEDLINE] 18: Tidsskr Nor Laegeforen. 2000 Sep 30;120(23):2796-8. Related Articles, Links [Why is insulin release from beta cells insufficient in type 2 diabetes?] [Article in Norwegian] Grill V. Institutt for abdominale fag, Regionsykehuset i Trondheim. valdemar.grill@medisin.ntnu.no Insulin secretion is finely tuned to tissue requirements by tight links to prevailing blood glucose levels. The normal regulation of insulin secretion is linked to glucose metabolism in the pancreatic beta-cell, a major but not exclusive signal for secretion being closure of K+ ATP-dependent channels in the cell membrane through an increase in the cytosolic ATP/ADP. Insulin secretion in type 2 diabetes is abnormal in several respects, due to genetic causes, but also due to the metabolic environment of the pancreatic beta-cells. This environment may be particularly important for the deterioration of insulin secretion, which occurs with increasing duration of diabetes. Factors of the environment with potential importance include over-stimulation, a negative effect of hyperglycaemia per se ("glucotoxicity"), and adverse effects of elevated fatty acids ("lipotoxicity"). A better understanding of the mechanisms behind these factors and of their clinical importance will pave the way for treatment which could preserve beta-cell function in type 2 diabetic patients. Publication Types: Review Review, Tutorial PMID: 11107928 [PubMed - indexed for MEDLINE] 19: J Ethnopharmacol. 1998 Aug;62(1):7-13. Related Articles, Links Pharmacological characterisation of the antihyperglycaemic properties of Tinospora crispa extract. Noor H, Ashcroft SJ. Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Headington, Oxford, UK. The efficacy of Tinospora crispa (Menispermaceae) extract for the treatment of diabetes has previously been verified in animal models. In order to substantiate the antidiabetic effect, we characterised the antihyperglycaemic properties by studying its effect on intestinal glucose absorption and glucose uptake into adipocytes. We also performed experiments to characterise in more detail the mechanism of T. crispa-evoked insulin release by challenging it with insulin secretory antagonists viz. adrenaline, somatostatin, verapamil and nifedipine. In addition, we also performed experiments to determine the effect of the extract on cAMP content. The results clearly showed that the antihyperglycaemic effect is not due to interference with intestinal glucose uptake or uptake of the sugar into the peripheral cells. Rather, the antihyperglycaemic effect of T. crispa is probably due to stimulation of insulin release via modulation of beta-cell Ca2+ concentration. That the insulinotropic effect of T. crispa is physiological suggests that the extract contains compounds which could be purified for use in the treatment of type II diabetes. PMID: 9720606 [PubMed - indexed for MEDLINE] 20: Br J Nutr. 1997 Aug;78(2):325-34. Related Articles, Links Pancreatic and extra-pancreatic effects of the traditional anti-diabetic plant, Medicago sativa (lucerne). Gray AM, Flatt PR. School of Biomedical Sciences, University of Ulster, Coleraine. Medicago sativa (lucerne) is used as a traditional plant treatment of diabetes. In the present study, administration of lucerne in the diet (62.5 g/kg) and drinking water (2.5 g/l) reduced the hyperglycaemia of streptozotocin-diabetic mice. An aqueous extract of lucerne (1 mg/ml) stimulated 2-deoxy-glucose transport (1.8-fold), glucose oxidation (1.7-fold) and incorporation of glucose into glycogen (1.6-fold) in mouse abdominal muscle. In acute 20 min tests, 0.25-1 mg/ml aqueous extract of lucerne evoked a stepwise 2.5-6.3-fold stimulation of insulin secretion from the BRIN-BD11 pancreatic B-cell line. This effect was abolished by 0.5 mM-diazoxide, and prior exposure to extract did not affect subsequent stimulation of insulin secretion by 10 mM-L-alanine, thereby negating a detrimental effect on cell viability. The effect of extract was potentiated by 16.7 mM-glucose and by 1 mM-3-isobutyl-1-methylxanthine. L-Alanine (10 mM) and a depolarizing concentration of KCl (25 mM) did not augment the insulin-releasing activity of lucerne. Activity of the extract was found to be heat stable and largely acetone insoluble, and was enhanced by exposure to acid and alkali (0.1 M-HCl and NaOH) but decreased 25% with dialysis to remove components with molecular mass < 2000 Da. Sequential extraction with solvents revealed insulin-releasing activity in both methanol and water fractions indicating a cumulative effect of more than one extract constituent. The results demonstrate the presence of antihyperglycaemic, insulin-releasing and insulin-like activity in the traditional antidiabetic plant, Medicago sativa. PMID: 9301421 [PubMed - indexed for MEDLINE] 21: Ala J Med Sci. 1969 Oct;6(4):455-63. Related Articles, Links Biological effects of Gymnema sylvestre fractions. II. Electrophysiology--effect of gymnemic acid on taste receptor response. Yackzan KS. PMID: 5363232 [PubMed - indexed for MEDLINE] 22: J Vet Med Sci. 1997 Apr;59(4):245-51. Related Articles, Links Suppression of glucose absorption by some fractions extracted from Gymnema sylvestre leaves. Shimizu K, Iino A, Nakajima J, Tanaka K, Nakajyo S, Urakawa N, Atsuchi M, Wada T, Yamashita C. Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo, Japan. Extracts containing gymnemic acids, which were extracted from the leaves of Gymnema sylvestre (GS) as nine fractions, were evaluated for their effects on a high K(+)-induced contraction of guinea-pig ileal longitudinal muscles, on glucose transport mediated by the difference of glucoseevoked transmural potential difference (delta PD) in the inverted intestine of guinea-pig and rat, and on blood glucose in rat. Among nine fractions obtained by high performance liquid chromatography from the extract, f-2 and f-4 strongly suppressed the high K(+)-induced contraction of the ileal muscle, f-3 and f-5 did so moderately, and f-8 and f-9 did so weakly, whereas the other fractions did not affect it. The degree of suppression of high K(+)-induced contraction by f-2 at 74% was almost the same as that of f-4 at 67%, at concentrations of 0.1 mg/ml. The suppressed contraction by f-2 or f-4 was recovered by adding 5.5 mM pyruvate. The delta PD increased by 5.5 mM glucose in the inverted intestines of guinea-pig and rat were equally suppressed by 0.1 mg/ml of f-2 or f-4 to 40%. In a rat sucrose tolerance test, f-2 and f-4 suppressed the elevation of blood glucose level. Both f-2 and f-4 suppressed the contraction of guinea-pig ileal longitudinal muscle, interfered with the increase in delta PD induced by glucose in the inverted intestines of guinea-pig and rat, and inhibited the elevation of blood glucose level. In conclusion, it is suggested that some of the extracts containing gymnemic acids from GS leaves suppress the elevation of blood glucose level by inhibiting glucose uptake in the intestine. PMID: 9152931 [PubMed - indexed for MEDLINE] 23: Ala J Med Sci. 1970 Jan;7(1):77-9. Related Articles, Links Biological effects of Gymnema sylvestre fractions. 3. Electrophysiology-in vitro gastric membrane findings. Yackzan KS. PMID: 5428555 [PubMed - indexed for MEDLINE] 24: Ala J Med Sci. 1977 Apr;14(2):150-6. Related Articles, Links Sensory effects of Gymnema sylvestre: implications of Mass action and chemical kinetics. Yackzan KS, Stoll PJ. PMID: 855895 [PubMed - indexed for MEDLINE] 25: Physiol Behav. 1970 Dec;5(12):1379-84. Related Articles, Links Effects of Gymnema sylvestre on complex tastes elicited by amino acids and sucrose. Meiselman HL, Halpern BP. PMID: 5524525 [PubMed - indexed for MEDLINE] 26: Physiol Behav. 1970 Aug;5(8):945-8. Related Articles, Links Human judgments of Gymnema sylvestre and sucrose mixtures. Meiselman HL, Halperin BP. PMID: 5522511 [PubMed - indexed for MEDLINE] J Vet Med Sci. 1997 Sep;59(9):753-7. Related Articles, Links Suppression of glucose absorption by extracts from the leaves of Gymnema inodorum. Shimizu K, Ozeki M, Tanaka K, Itoh K, Nakajyo S, Urakawa N, Atsuchi M. Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo, Japan. Gymnema sylvestre (GS) is one of the Asclepiad strains that grows in South-east Asia. Their therapeutic effects for treating diabetes mellitus, rheumatic arthritis and gout have been well known for a long time. However, the problem is that GS suppresses sweetness and tastes bitter. For this study, we chose Gymnema inodorum (GI) instead of GS, since it has an advantage that it does not suppress sweetness nor is it bitter in taste. In this paper, effects of glucose availability of some saponin fractions (F-I to F-IV) extracted from GI leaves, which were obtained by highperformance liquid chromatography were studied on a high K(+)-induced contraction of guineapig intestinal smooth muscle, O2 consumption on guinea-pig ileum, glucose-evoked transmural potential difference (delta PD) of guinea-pig everted intestine and blood glucose level in glucose tolerance tests on rats. The extracts of GI leaves suppressed the intestinal smooth muscle contraction, decreased the O2 consumption, inhibited the glucose evoked-transmural potential, and prevented the blood glucose level. Our studies suggest that the component of GI inhibits the increase in the blood glucose level by interfering with the intestinal glucose absorption process. PMID: 9342697 [PubMed - indexed for MEDLINE] 2: J Smooth Muscle Res. 1996 Oct;32(5):219-28. Related Articles, Links [Inhibitory effects of glucose utilization by gymnema acids in the guinea-pig ileal longitudinal muscle] [Article in Japanese] Shimizu K, Abe T, Nakajyo S, Urakawa N, Atsuchi M, Yamashita C. Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo, Japan. Two substances identified as ((3 beta, 4 alpha, 16 beta, 21 beta, 22 alpha)-21-tigloxy-16, 22, 23, 28-tetrahydroxyolean-12-en-3-yl-beta D-glucopyranosiduronic acid) (GA1) and ((3 beta, 4 alpha, 16 beta, 21 beta, 22 alpha)-21-(2-methylbutyroxy)-16, 22, 23, 28-tetrahydroxyolean-12-en-3-ylbeta-D-glucopyranosiduronic acid) (GA2) identified among the gymnemic acids are triterpene glycosides extracted from Gymnema sylvestre leaves. We examined the effects of GA1 or GA2 on high K(+)-induced contraction in the guinea-pig longitudinal muscle. A sustained muscle contraction induced by hyperosmotically added 65.4 mM KCI (H-65K+) was suppressed by GA1 or GA2 (7.7 x 10(-5) M). Simultaneous measurements of reduced pyridine nucleotide (PNred) or oxidized flavin protein (FPox) by the fluorescence technique and of contractile force revealed that GA1 and GA2 reduced the increase of PNred fluorescence and contractile force induced by H65K+, whereas FPox fluorescence induced by it further increased. Reduced muscle contraction induced by GA1 or GA2 was restored by 5.5 mM pyruvate. Simultaneous measurements of intracellular Ca2+ [Ca2+]1 level and contractile force indicated that [Ca2+]1 level, which increased by H-65K+, hardly changed with GA1 and GA2. In summary, both GA1 and GA2, which are among the gymnemic acids, suppressed high K(+)-induced contraction in the guinea-pig ileal longitudinal muscle. The difference between these two gymnemic acids was not significant. The inhibitory effect of GA1 and GA2 on smooth muscle were assumed to be a result of inhibiting glucose uptake, which is an energy source of the muscle, whereas the inhibitory mechanisms were probably not mediated by Ca2+. PMID: 8985922 [PubMed - indexed for MEDLINE] 3: Jpn J Pharmacol. 2001 Jun;86(2):223-9. Related Articles, Links Structure-activity relationships of triterpenoid derivatives extracted from Gymnema inodorum leaves on glucose absorption. Shimizu K, Ozeki M, Iino A, Nakajyo S, Urakawa N, Atsuchi M. Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Musashino-shi, Tokyo, Japan. The leaves of Gymnema inodorum (GI) have been known to be effective for some diseases including diabetes mellitus, rheumatic arthritis and gout. The crude saponin mixtures extracted from GI leaves inhibited glucose absorption in the isolated intestinal tract and suppressed the increased blood glucose in rats. In this study, we examined the relationship between chemical structure and pharmacological activity of the four components from GI leave extracts (GiA-1, GiA-2, GiA-5 and GiA-7). These components were the derivatives of (3beta,4alpha,16beta)- 16,23,28-trihydroxyolean-12-en-3-yl-beta-D-glucopyranosiduroic acid. GiA-2, GiA-5 and GiA-7 that have suppressive effects on the high K+-induced contraction, an increase in deltaPD and the increased blood glucose level in the glucose tolerance test have -H at the 21st position and CH2OH at 4beta of aglycon. On the other hand, GiA-1 that does not have any effects on the three parameters mentioned above has -H at the 21st position and -CH3 at 4beta of aglycon. In conclusion, it is suggested that the inhibitory effect of triterpenoids in Gymnema leaves on glucose absorption from the intestinal tract relies on -CH2OH at 4beta. PMID: 11459125 [PubMed - indexed for MEDLINE] 4: Chem Pharm Bull (Tokyo). 1997 Dec;45(12):2034-8. Related Articles, Links Medicinal foodstuffs. X. Structures of new triterpene glycosides, gymnemosides-c, -d, -e, and -f, from the leaves of Gymnema sylvestre R. Br.: influence of gymnema glycosides on glucose uptake in rat small intestinal fragments. Yoshikawa M, Murakami T, Matsuda H. Kyoto Pharmaceutical University, Japan. Following the characterization of gymnemosides-a and -b, new triterpene glycosides, gymnemosides-c, -d, -e, and -f, were isolated from the leaves of Gymnema (G.) sylvestre R. BR. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence as follows: 21-O-benzoyl-28-O-acetylgymnemagenin 3-O-beta-D-glucopyranosiduronic acid (gymnemoside-c), 23-O-[beta-D-xylopyranosyl (1-->6)-beta-D-glucopyranosyl (1-->6)-beta-Dglucopyranosyl] gymnestrogenin (gymnemoside-d), 23-O-[beta-D-xylopyranosyl (1-->6)-beta-Dglucopyranosyl (1-->6)-beta-D- glucopyranosyl]-28-O-[beta-D-glucopyranosyl (1-->6)-beta-Dglucopyranosyl] 23-hydroxylongispinogenin (gymnemoside-e), 23-O-[beta-D-xylopyranosyl (1->6)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl]-28-O-[beta-O-glucopyranosyl (1->6)-beta-D-glucopyranosyl] 3 beta,16 beta,23,28-tetrahydroxyolean-18-ene (gymnemoside-f). The inhibitory effects of gymnemosides-c, -d, -e, and -f and principal triterpene glycosides from G. sylvestre on glucose uptake in rat small intestinal fragments were examined, and gymnemic acids II, III, and IV, gymnemasaponin V, and gymnemoside-f were found to exhibit the inhibitory activity. PMID: 9433774 [PubMed - indexed for MEDLINE] 5: Chem Pharm Bull (Tokyo). 1997 Oct;45(10):1671-6. Related Articles, Links Medicinal foodstuffs. IX. The inhibitors of glucose absorption from the leaves of Gymnema sylvestre R. BR. (Asclepiadaceae): structures of gymnemosides a and b. Yoshikawa M, Murakami T, Kadoya M, Li Y, Murakami N, Yamahara J, Matsuda H. Kyoto Pharmaceutical University, Japan. Although the glycosidic fraction from the dried leaves of Gymnema sylvestre R. BR., gymnemic acid, was reported to be effective for diabetes, it showed little inhibitory activity on the increase of serum glucose level in oral glucose-loaded rats. From the glycosidic fraction, six triterpene glycosides, gymnemosides a, b, c, d, e, and f, were isolated together with nine known triterpene glycosides. The structures of gymnemosides a and b were determined on the basis of chemical and physicochemical evidence as 21-O-tigloyl-22-O-acetylgymnemagenin 3-O-beta-D- glucopyranosiduronic acid and 16-O-acetyl-21-O-tigloylgymnemagenin 3-O-beta-Dglucopyranosiduronic acid, respectively. In addition, an acetyl group linked to the 16- or 22hydroxyl group in gymnemosides a and b was found to migrate easily to the primary 28-hydroxyl group, while the acyl migration from the 28-position was rarely observed. The inhibitory activity of each triterpene glycoside from gymnemic acid was examined to determine its impact on the increase of serum glucose level in oral glucose-loaded rats. Gymnemoside b and gymnemic acids III, V, and VII were found to exhibit a little inhibitory activity against glucose absorption, but the principal constituents, gymnemic acid I and gymnemasaponin V, lacked this activity. PMID: 9353896 [PubMed - indexed for MEDLINE] 6: J Asian Nat Prod Res. 2000;2(4):321-7. Related Articles, Links Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice. Sugihara Y, Nojima H, Matsuda H, Murakami T, Yoshikawa M, Kimura I. Department of Chemical Pharmacology, Toyama Medical and Pharmaceutical University, Sugitani, Japan. We investigated the antihyperglycemic action of a crude saponin fraction and five triterpene glycosides (gymnemic acids I-IV and gymnemasaponin V) derived from the methanol extract of leaves of Gymnema sylvestre R. BR. (Asclepiadaceae) in streptozotocin (STZ)-diabetic mice. The saponin fraction (60mg/kg) reduced blood glucose levels 2 4h after the intraperitoneal administration. Gymnemic acid IV, not the other 4 glycosides at doses of 3.4-13.4mg/kg reduced the blood glucose levels by 13.5-60.0% 6h after the administration comparable to the potency of glibenclamide, and did not change the blood glucose levels of normal mice. Gymnemic acid IV at 13.4 mg/kg increased plasma insulin levels in STZ-diabetic mice. Gymnemic acid IV (1 mg/mL) did not inhibit alpha-glycosidase activity in the brush border membrane vesicles of normal rat small intestines. These results indicate that insulin-releasing action of gymnemic acid IV may contribute to the antihyperglycemic effect by the leaves of G. sylvestre. Gymnemic acid IV may be an anti-obese and antihyperglycemic pro-drug. PMID: 11249615 [PubMed - indexed for MEDLINE] 7: J Ethnopharmacol. 1999 Dec 15;68(1-3):307-14. Related Articles, Links Improving effects of the extracts from Eugenia uniflora on hyperglycemia and hypertriglyceridemia in mice. Arai I, Amagaya S, Komatsu Y, Okada M, Hayashi T, Kasai M, Arisawa M, Momose Y. Central Research Laboratories, Tsumura & Company, Ibaraki, Japan. arai_ichirou@mail.tsumura.co.jp EtOH (70%) extracts from the leaves of Eugenia uniflora were separated into six fractions with different polarity and molecular size, i.e. NP-1-NP-6. In an oral glucose tolerance test, NP-1 and 4 inhibited the increase in plasma glucose level. However, in an intraperitoneal glucose tolerance test, such an inhibitory effect was not seen. Thus, the effects of NP-1 and 4 were apparently due to the inhibition of glucose absorption from the intestine. In a sucrose tolerance test, all fractions inhibited the increase in plasma glucose level. In an oral corn oil tolerance test, NP-3 and 4 showed an inhibitory effect on the increase in plasma triglycerides level. On the other hand, NP-3, 4, 5 and 6 inhibited maltase and sucrase activities and all fractions except for NP-1 showed an inhibitory effect on lipase activity dose-dependently. The inhibition of the increase in plasma glucose level by NP-3, 4, 5 and 6 in the oral sucrose tolerance test and the inhibition of the increase in plasma triglycerides by NP-3 and 4 in the oral corn oil tolerance test were apparently due to the inhibition of the decomposition of carbohydrates and fats in the intestine, respectively. PMID: 10624893 [PubMed - indexed for MEDLINE] 8: J Nutr. 1999 Jun;129(6):1214-22. Related Articles, Links Fecal steroid excretion is increased in rats by oral administration of gymnemic acids contained in Gymnema sylvestre leaves. Nakamura Y, Tsumura Y, Tonogai Y, Shibata T. Division of Food Chemistry, National Institute of Health Sciences, Osaka Branch, 1-1-43, Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan. Gymnemic acids are the saponins with a triterpenoid structure contained in Gymnema sylvestre leaves and have the hypoglycemic effects. In spite of the cholesterol-binding properties of saponins, the effect of gymnemic acids on cholesterol metabolism has not been elucidated to date. We investigated the effects of gymnemic acids on fecal steroid excretion in rats. Three kinds of extracts from Gymnema sylvestre leaves, extract (GSE), acid precipitate (GSA) and column fractionate (GSF), of which the gymnemagenin (an aglycone of gymnemic acids) concentrations are 58.87, 161.6, and 363.3 mg/g respectively, were used for the experiments. These were administered to rats orally at the dose of 0.05-1.0 g/kg for 22 d. Rats were given free access to water and nonpurified diet without cholesterol, and the differences in fecal excretion of steroids and gymnemic acids were investigated. Although there were no significant effects of GSE, GSA and GSF decreased body weight gain and food intakes in a dose-dependent manner (P < 0.01). GSF (1.0 g/kg) significantly increased fecal excretion of neutral steroids and bile acids in a dosedependent manner (P < 0.05), especially those of cholesterol and cholic acid (CA)-derived bile acids. The increases in fecal steroid excretion of cholesterol, total neutral steroids, total bile acids and CA-related bile acids were acute and significantly correlated with fecal gymnemagenin levels (r2 = 0.2316-0.9861, P < 0. 05). These results demonstrated for the first time that a high dose of gymnemic acids increases fecal cholesterol and CA-derived bile acid excretion. Further studies are needed to clarify the effect of gymnemic acids on cholesterol metabolism. PMID: 10356090 [PubMed - indexed for MEDLINE] 9: Methods Find Exp Clin Pharmacol. 1997 Oct;19(8):515-20. Related Articles, Links Triterpenoid compounds from Araujia sericifera B. Effects on the isolated guinea pig ileum. Lopez de Medrano-Villar MJ, Bello R, Esplugues J, Primo-Yufera E, Primo-Millo J. Departamento de Biotecnologia, Universidad Politecnica de Valencia, Spain. Different fractions from the methanol insoluble extract of Araujia sericifera were obtained by chromatography and evaluated for their antihistaminic effects on guinea pig ileum in vitro. In order to determine the compounds responsible for the pharmacological effects observed, separation of the components from the active fraction was performed using HPLC. PMID: 9442473 [PubMed - indexed for MEDLINE] 10: Pharmazie. 2003 Jun;58(6):413-5. Related Articles, Links Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones. Gholap S, Kar A. Thyroid Research Unit, School of Life Sciences, D. A. University, Khandwa Road, Indore, India. The efficacy of Inula racemosa (root) and Gymnema sylvestre (leaf) extracts either alone or in combination was evaluated in the amelioration of corticosteroid-induced hyperglycaemia in mice. Simultaneously thyroid hormone levels were estimated by radio-immunoassay (RIA) in order to ascertain whether the effects are mediated through thyroid hormones or not. While the corticosteroid (dexamethasone) administration increased the serum glucose concentration, it decreased serum concentrations of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Administration of the two plant extracts either alone or in combination decreased the serum glucose concentration in dexamethasone induced hyperglycaemic animals. However, the administration of Inula racemosa and Gymnema sylvestre extracts in combination proved to be more effective than the individual extracts. These effects were comparable to a standard corticosteroid-inhibiting drug, ketoconazole. As no marked changes in thyroid hormone concentrations were observed by the administration of any of the plant extracts in dexamethasone treated animals, it is further suggested that these plant extracts may not prove to be effective in thyroid hormone mediated type II diabetes, but for steroid induced diabetes. PMID: 12857006 [PubMed - indexed for MEDLINE] 11: Biosci Biotechnol Biochem. 1998 Jun;62(6):1225-7. Related Articles, Links Suppression by water extracts of Sophora plants of sucrose-induced hyperglycemia in rats and inhibition of intestinal disaccharidases in vitro. Shi HC, Huang QY, Yamaji R, Inui H, Fujita T, Miyatake K, Nakano Y, Tada T, Nishimura K. Department of Applied Biological Chemistry, Osaka Prefecture University, Japan. Partially purified hot-water extracts of the roots of plants of the Sophora family suppressed the increase in blood glucose concentration of rats in the oral sugar tolerance test. The extracts also inhibited rat intestinal sucrase and maltase. The most potent sample was about 15 times more active than catechin, a positive control, in these experiments. PMID: 9692207 [PubMed - indexed for MEDLINE] 12: J Ethnopharmacol. 2000 Sep;72(1-2):129-33. Related Articles, Links Hypoglycemic effect of Equisetum myriochaetum aerial parts on streptozotocin diabetic rats. Andrade Cetto A, Wiedenfeld H, Revilla MC, Sergio IA. Biological Department, Science School, National University of Mexico UNAM, DF., 04510 Mexico, Mexico. The hypoglycemic effect of water as well as butanolic extracts prepared from aerial parts of Equisetum myriochaetum (Equisetaceae) was examined in streptozotocin induced diabetic rats. A single oral administration of the water extract (WE) at doses of 7 and 13 mg/kg and of the butanol extract (BE) at doses of 8 and 16 mg/kg significantly (P<0.001) lowered the plasma glucose levels in diabetic rats after three hours of the administration. As a reference drug glibenclamide was used and showed, at a dose of 3 mg/kg, similar hypoglycemic effect like the tested extracts. Three kaempferol glucosides and one caffeoyl glucoside were isolated from the drug and were shown to be the main constituents in both extracts. PMID: 10967463 [PubMed - indexed for MEDLINE] 13: Biol Pharm Bull. 2001 Jun;24(6):713-7. Related Articles, Links Effect of administration with the extract of Gymnema sylvestre R. Br leaves on lipid metabolism in rats. Shigematsu N, Asano R, Shimosaka M, Okazaki M. Biosci. Textile Technol., Shinshu University, Ueda, Nagano, Japan. noshigematsu@fancl.co.jp Extract of Gymnema sylvestre R. Br leaves (GE) was orally administered once a day to rats fed a high fat diet or normal fat diet for 3 weeks to investigate its influence on lipid metabolism. As a result, GE did not influence body weight gain or feed intake in both diet groups during the experimental period. The apparent fat digestibility was significantly decreased by GE in both diet groups for the last 2 weeks of the experimental period, though not the apparent protein digestibility. In addition, the excretion of neutral sterols and acid steroids into feces was increased by GE in both diet groups. Furthermore, GE decreased the total cholesterol and triglyceride levels in serum. On the other hand, blood lecithin-cholesterol acyltransferase (LCAT) activity was increased by GE. Moreover, it was suggested that GE influenced cecal fermentation and that propionic acid and acetic acid contents in cecum were significantly increased by GE. Consequently, it was suggested that GE improved serum cholesterol and triglyceride levels through influence over a wide range of lipid metabolism in rats. PMID: 11411567 [PubMed - indexed for MEDLINE] 14: J Pharm Pharmacol. 1999 Nov;51(11):1321-4. Related Articles, Links Evaluation of the anti-diabetic property of Morinda lucida leaves in streptozotocin-diabetic rats. Olajide OA, Awe SO, Makinde JM, Morebise O. Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria. mailbox@ibadan.skannet.com The hypoglycaemic and anti-hyperglycaemic activities of a methanol extract of Morinda lucida Benth. (Rubiaceae) leaves were studied in normal and streptozotocin-diabetic rats. In normal rats, the extract demonstrated a significant (P < 0.05) and dose-dependent hypoglycaemic activity within 4 h after oral administration. The plasma glucose level of 400 mg kg(-1) of the extract at 4 h was 42.5 +/- 0.4 mg/100 mL (control 67.4 +/- 1.2 mg/100 mL). After 12 h, the plasma glucose level of rats administered 50, 100, 200 or 400 mg kg(-1) extract fell to 51.9 +/- 1.2, 47.3 +/- 0.8, 43.1 +/- 0.4 and 40.0 +/- 0.5 mg/100 mL, respectively. In hyperglycaemic rats, the extract produced a significant (P < 0.05) anti-diabetic effect from day 3 after oral administration, with 400 mg kg(-1) extract-treated animals having a plasma glucose level of 248.7 +/- 5.3 mg/100 mL compared with glibenclamide (10 mg kg(-1))-treated animals with a plasma glucose level of 251.5 +/- 5.8 mg/100 mL. These results suggest that the leaves of Morinda lucida have a strong glucose lowering property when administered to streptozotocin-treated rats. PMID: 10632091 [PubMed - indexed for MEDLINE] 15: Gen Pharmacol. 1998 Sep;31(3):495-6. Related Articles, Links Possible mechanism of antihyperglycemic effect of Gymnema sylvestre leaf extract, part I. Chattopadhyay RR. Indian Statistical Institute, Calcutta. 1. Effect of water soluble fraction of alcoholic extract of G. sylvestre leaves on glycogen content by isolated rat hemidiaphragm was studied in normal and glucose fed hyperglycemic rats. 2. The leaf extract by itself failed to alter the hepatic glycogen content in normal rats. 3. In glucose fed rats, the leaf extract lowered the glycogen content of the tissue significantly (P<0.05) and this was further lowered when both exogenous insulin and leaf extract was administered. 4. The results are discussed. PMID: 9703226 [PubMed - indexed for MEDLINE] 16: Biol Pharm Bull. 2001 Jun;24(6):643-9. Related Articles, Links Effect of long term-administration with Gymnema sylvestre R. BR on plasma and liver lipid in rats. Shigematsu N, Asano R, Shimosaka M, Okazaki M. Biosci. Textile Technol., Shinshu University, Ueda, Nagano, Japan. noshigematsu@fancl.co.jp Extract of Gymnema sylvestre leaves was administered to rats receiving either a high fat diet or normal fat diet for 10 weeks to investigate its influence on plasma and liver lipids and on visceral fat accumulation. In addition, its effect was compared with those of chitosan and the influence of combined use of these two substances was also evaluated. Within the high fat diet groups, the extract suppressed body weight gain and accumulation of liver lipids to the same extent as chitosan and the combined use. In addition, intraperitoneal fat and fat drop vacuoles on the epithelium of renal tubules, noted in the high fat diet group, were scattered by administration of the extract with the same results as for chitosan and combined use. Within the normal fat diet groups, plasma triglyceride levels decreased by administration of the extract, with similar results as chitosan and combined use. Concerning plasma total cholesterol, there was no decreasing effects with the extract, as found with chitosan and combined use. However, the effect of chitosan on plasma total cholesterol tended to be enhanced when used in combination with the extract. In addition, long-term administration of the extract did not show any influence on hematological and blood chemical parameters. PMID: 11411552 [PubMed - indexed for MEDLINE] 17: J Ethnopharmacol. 1986 Nov;18(2):143-6. Related Articles, Links Effect of feeding Gymnema sylvestre leaves on blood glucose in beryllium nitrate treated rats. Prakash AO, Mathur S, Mathur R. The feeding of powdered leaves of Gymnema sylvestre in the diet of rats for 10 days prior and 15 days after i.v. beryllium nitrate significantly protected the animals from the full fall of blood glucose seen in rats receiving beryllium nitrate alone. The feeding of the leaves for 25 days to normal rats did not alter blood glucose significantly. The leaves may contain a principle that could be useful as a prophylactic against beryllium toxicity. PMID: 3560992 [PubMed - indexed for MEDLINE] 18: Helv Chim Acta. 1968;51(6):1235-42. Related Articles, Links [Gymnestrogenin, a new pentahydroxytriterpene from the leaves of Gymnema sylvestre R.Br.] [Article in German] Stocklin W. PMID: 5680734 [PubMed - indexed for MEDLINE] 19: Comp Biochem Physiol. 1968 Jun;25(3):1091-7. Related Articles, Links Failure of Gymnema extract to inhibit the sugar receptors of two invertebrates. Larimer JL, Oakley B. PMID: 5758866 [PubMed - indexed for MEDLINE] 20: Life Sci. 1969 May 1;8(9):537-43. Antisweet activity of gymnemic acid A1 and its derivatives. Kurihara Y. Related Articles, Links PMID: 5791706 [PubMed - indexed for MEDLINE] 1: Isr J Med Sci. 1985 Jun;21(6):540-2. Related Articles, Links Hypoglycemic and life-prolonging properties of Gymnema sylvestre leaf extract in diabetic rats. Srivastava Y, Nigam SK, Bhatt HV, Verma Y, Prem AS. PMID: 4019152 [PubMed - indexed for MEDLINE] 2: J Ethnopharmacol. 1990 Oct;30(3):281-94. Related Articles, Links Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Department of Biochemistry, University of Madras, India. GS4, a water-soluble extract of the leaves of Gymnema sylvestre, was administered (400 mg/day) to 27 patients with insulin-dependent diabetes mellitus (IDDM) on insulin therapy. Insulin requirements came down together with fasting blood glucose and glycosylated haemoglobin (HbA1c) and glycosylated plasma protein levels. While serum lipids returned to near normal levels with GS4 therapy, glycosylated haemoglobin and glycosylated plasma protein levels remained higher than controls. IDDM patients on insulin therapy only showed no significant reduction in serum lipids, HbA1c or glycosylated plasma proteins when followed up after 10-12 months. GS4 therapy appears to enhance endogenous insulin, possibly by regeneration/revitalisation of the residual beta cells in insulin-dependent diabetes mellitus. Publication Types: Clinical Trial PMID: 2259216 [PubMed - indexed for MEDLINE] 3: Planta Med. 1996 Oct;62(5):440-3. Related Articles, Links Hypoglycemic effect of the rhizomes of Polygala senega in normal and diabetic mice and its main component, the triterpenoid glycoside senegin-II. Kako M, Miura T, Nishiyama Y, Ichimaru M, Moriyasu M, Kato A. Suzuka University of Medical Science and Technology, Mie, Japan. The hypoglycemic effect of the rhizomes of Polygala senega L. var. latifolia Torrey et Gray (Polygalaceae) was investigated in normal and KK-Ay mice, one of the model animals of noninsulin dependent diabetes mellitus (NIDDM). The n-butanol extract of senega rhizomes (SN) (5 mg/kg) reduced the blood glucose of normal mice from 191 +/- 3 to 120 +/- 3 mg/dl 4 hours after intraperitoneal administration (P < 0.001), and also showed a significant decrease in the glucose level of KK-Ay mice from 469 +/- 38 to 244 +/- 14 mg/dl under similar conditions (P < 0.001). But streptozotocin-induced diabetic mice did not experience a change in the blood glucose after administration of SN. We propose that the hypoglycemic effect of SN occurs without altering the insulin concentration. Moreover, SN needs the presence of insulin in order to act. In addition, one of the active components of the hypoglycemic effect was identified as a triterpenoid glycoside, senegin-II. PMID: 8923811 [PubMed - indexed for MEDLINE] 4: Planta Med. 1994 Jun;60(3):244-7. Related Articles, Links Hypoglycemic and antihyperglycemic effects of Zizyphus spina-christi in rats. Glombitza KW, Mahran GH, Mirhom YW, Michel KG, Motawi TK. Institute of Pharmaceutical Biology, Bonn University, Federal Republic of Germany. Zizyphus is one of the plants commonly used in Egyptian folk medicine for the treatment of different diseases. The present study aims to investigate the effect of the butanol extract of Zizyphus spina-christi leaves as well as christinin-A, its principle saponin glycoside, in normal and streptozotocin-diabetic rats. In normal rats, treatment in both cases for one and four weeks produced insignificant changes in all studied parameters. However, in diabetic rats, both treatments significantly reduced serum glucose level, liver phosphorylase and glucose-6phosphatase (G-6-pase) activities, and significantly increased serum pyruvate level and liver glycogen content after 4 weeks treatment. There was also marked improvement in glucose utilization in diabetic rats in both cases. Serum insulin and pancreatic cAMP levels showed significant increases in diabetic rats treated for a period of 4 weeks with the butanol extract. PMID: 8073092 [PubMed - indexed for MEDLINE] 5: Fitoterapia. 2002 Apr;73(2):156-9. Related Articles, Links Hypoglycemic activity of Abutilon indicum leaf extracts in rats. Seetharam YN, Chalageri G, Setty SR, Bheemachar. Biosystematics and Medicinal Plant Laboratory, Department of Botany, Gulbarga University, 585 106, Gulbarga, India. Alcohol and water extracts of Abutilon indicum leaves (400 mg/kg, p.o.) showed significant hypoglycemic effect in normal rats 4 h after administration (23.10% and 26.95%, respectively). PMID: 11978431 [PubMed - indexed for MEDLINE] 6: J Ethnopharmacol. 1988 Jan;22(1):81-90. Effect of Cassia alata leaf extract on hyperglycemic rats. Palanichamy S, Nagarajan S, Devasagayam M. Related Articles, Links Department of Chemistry, Bharathidasan University, Tiruchirapalli, India. The oral effectiveness of Cassia alata leaf extract on streptozotocin-induced hyperglycemia in rats has been studied and the results compared with glybenclamide. While the extract has no effect on glucose levels in normoglycemic animals, it reduced the blood sugar value in streptozotocininduced hyperglycemic animals. PMID: 3352288 [PubMed - indexed for MEDLINE] 7: J Ethnopharmacol. 1998 Feb;60(1):27-32. Related Articles, Links Hypoglycemic effect of the water extract of Piper sarmentosum in rats. Peungvicha P, Thirawarapan SS, Temsiririrkkul R, Watanabe H, Kumar Prasain J, Kadota S. Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. The hypoglycemic effect of the water extract of the whole plant of Piper sarmentosum Roxb. (Piperaceae, Thai name: Chaplu) was examined in normal and streptozotocin-diabetic rats. In an oral glucose tolerance test, a single oral administration of the water extract at doses of 0.125 and 0.25 g/kg significantly lowered the plasma glucose level in the normal rats. A reference drug, glibenclamide, at a dose of 5 mg/kg (per os, p.o.) also showed a significant hypoglycemic effect in the normal rats. In contrast, a single oral administration of the water extract at these doses and glibenclamide did not significantly lower the plasma glucose level in the diabetic rats. However, the repeated oral administration of the water extract at a dose of 0.125 g/kg for 7 days produced a significant hypoglycemic effect in the diabetic rats. Glibenclamide (5 mg/kg, p.o.) also caused significant hypoglycemia in the diabetic rats. These results demonstrated that the water extract of whole plant of Piper sarmentosum has a hypoglycemic effect in rats. PMID: 9533429 [PubMed - indexed for MEDLINE] 8: Biomed Environ Sci. 1999 Sep;12(3):222-6. Related Articles, Links A preliminary investigation of the possible hypoglycemic activity of Hibiscus rosa-sinensis. Sachdewa A, Khemani LD. Department of Chemistry, Faculty of Science, Dayalbagh Educational Institute, Agra, India. The hypoglycemic activity of an ethanol extract of Hibiscus rosa-sinensis was studied in glucose located rats. After a single dose of the extract, a slight but insignificant hypoglycemic effect was observed at 30 and 90 min. At 120 min it was mild but significant. After repeated administration of the extract (once a day for seven consecutive days) a statistically significant (P < 0.001) reduction in blood glucose levels was observed at 30, 90 and 120 min after glucose loading. The average hypoglycemic activity, after repeated administration of 250 mg kg-1 leaf extract was 81%, under similar conditions average activity of tolbutamide was 96%. At 250 mg.kg-1 the efficacy of the extract was found to be 84% of tolbutamide (100 mg.kg-1). Repeated treatment of animals either with tolbutamide a sulphonylurea or H. rosa-sinensis caused a 2-3-fold improvement in glucose tolerance as compared to those receiving only once. These data suggest that the leaf extract acts like tolbutamide and the mechanism of action may be a stimulation of pancreatic beta cells to produce more insulin or an increase of the glycogen deposition in liver. It appears that the active principle in the tested extract has the sulphonylurea skeleton in which-SO2-NH-CO-group and the substituents (S1 and S2) may be the possible active sites responsible for its hypoglycemic activity. PMID: 10674186 [PubMed - indexed for MEDLINE] 9: J Med Food. 2003 Spring;6(1):43-9. Related Articles, Links Effect of Gymnema montanum on blood glucose, plasma insulin, and carbohydrate metabolic enzymes in alloxan-induced diabetic rats. Ananthan R, Latha M, Pari L, Ramkumar KM, Baskar CG, Bai VN. Department of Botany, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India. The effects of Gymnema montanum, an endangered plant used in the ancient period of India, on blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in alloxan diabetic rats. Administration of alcoholic extract of G. montanum leaves (50, 100, 200 mg/kg body weight) to alloxan diabetic rats for 3 weeks reduced the blood glucose level. Administration of G. montanum leaf extract (GLEt) at 200 mg/kg body weight significantly decreased the blood glucose levels and significantly increased the plasma insulin levels. This clearly shows the antidiabetic efficacy of GLEt, which was better than that of glibenclamide. PMID: 12804019 [PubMed - indexed for MEDLINE] 10: J Ethnopharmacol. 1983 Mar;7(2):205-34. Related Articles, Links Enzyme changes and glucose utilisation in diabetic rabbits: the effect of Gymnema sylvestre, R.Br. Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER. The administration of the dried leaf powder of Gymnema sylvestre regulates the blood sugar levels in alloxan diabetic rabbits. G. sylvestre therapy not only produced blood glucose homeostasis but also increased the activities of the enzymes affording the utilisation of glucose by insulin dependent pathways: it controlled phosphorylase levels, gluconeogenic enzymes and sorbitol dehydrogenase. The uptake and incorporation of [14C] glucose into the glycogen and protein are increased in the liver, kidney and muscle in G. sylvestre administered diabetic animals when compared to the untreated diabetic animals. Pathological changes initiated in the liver during the hyperglycemic phase are reversed by controlling hyperglycemia by G. sylvestre. G. sylvestre, a herb used for the control of diabetes mellitus in several parts of India, appears to correct the metabolic derangements in diabetic rabbit liver, kidney and muscle. PMID: 6865451 [PubMed - indexed for MEDLINE] 11: J Ethnopharmacol. 2001 Feb;74(2):125-32. Related Articles, Links Hypoglycemic effect of the water extract of Smallantus sonchifolius (yacon) leaves in normal and diabetic rats. Aybar MJ, Sanchez Riera AN, Grau A, Sanchez SS. Departamento de Biologia del Desarrollo, INSIBIO/CONICET, Universidad Nacional de Tucuman (UNT), Chacabuco 461, 4000-San Miguel de Tucuman, Tucuman, Argentina The hypoglycemic effect of the water extract of the leaves of Smallantus sonchifolius (yacon) was examined in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Ten-percent yacon decoction produced a significant decrease in plasma glucose levels in normal rats when administered by intraperitoneal injection or gastric tube. In a glucose tolerance test, a single administration of 10% yacon decoction lowered the plasma glucose levels in normal rats. In contrast, a single oral or intraperitoneal administration of yacon decoction produced no effect on the plasma glucose levels of STZ-induced diabetic rats. However, the administration of 2% yacon tea ad libitum instead of water for 30 days produced a significant hypoglycemic effect on STZinduced diabetic rats. After 30 days of tea administration, diabetic rats showed improved body (plasma glucose, plasma insulin levels, body weight) and renal parameters (kidney weight, kidney to body weight ratio, creatinine clearance, urinary albumin excretion) in comparison with the diabetic controls. Our results suggest that yacon water extract produces an increase in plasma insulin concentration. PMID: 11167030 [PubMed - indexed for MEDLINE] 12: J Ethnopharmacol. 2002 May;80(2-3):203-6. Related Articles, Links Effect of Cassia auriculata Linn. on serum glucose level, glucose utilization by isolated rat hemidiaphragm. Sabu MC, Subburaju T. Amala Cancer Research Center, Amala Nagar, Thrissur 680 553, Kerala, India. sabu_mc@rediff.com An aqueous leaf extract of Cassia auriculata (C. auriculata) was found to lower the serum glucose level in normal rats. Maximum reduction in serum glucose level was observed after 4 h at a dose levels of 100, 200, 400 mg/kg body weight of the extract. In normal rats the serum glucose level reduction at 4th h was 23% by 100 mg/kg body weight and 31% by 200 mg/kg body weight. In alloxan-induced diabetic rats, chronic administration of the extract significantly reduced the serum glucose level from third day to till the end of the experiment. The extract was also found to inhibit the body weight reduction induced by alloxan administration. Glucose uptake and glycogen deposition studies suggest that C. auriculata leaf extract probably has no direct insulin like effect which can enhance the peripheral utilization of glucose. PMID: 12007712 [PubMed - indexed for MEDLINE] 13: Biol Pharm Bull. 1996 Mar;19(3):364-6. Related Articles, Links Hypoglycemic effect of water extract of the root of Pandanus odorus RIDL. Peungvicha P, Thirawarapan SS, Watanabe H. Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. Hypoglycemic effect of water extract of the root of Pandanus odorus RIDL. (Thai name: Toeihom, Pandanaceae) was examined in normal and streptozotocin-diabetic rats. In the hypoglycemic test without glucose load, an administration of the extract at doses of 0.125-0.5g/kg p.o. did not affect significantly the plasma glucose level in normal rats, whereas the extract significantly lowered the plasma glucose level at a dose of 0.5g/kg p.o. in diabetic rats. In oral glucose tolerance test, an administration of the extract at a dose of 0.5g/kg p.o. significantly lowered the plasma glucose level in normal rats. The extract at doses of 0.5 and 1.0g/kg p.o. also significantly lowered the plasma glucose level in diabetic rats. A reference drug, glibenclamide at a dose of 5 mg/kg p.o. showed a significant hypoglycemic effect in both normal and diabetic rats. Repeated administration of the extract at doses of 0.25 and 0.5 g/kg p.o. for 7d produced a significant hypoglycemic effect in diabetic rats. Glibenclamide (5 mg/kg p.o.) also caused a significant hypoglycemia in the diabetic rats. LD50 (95% confidence limit) after intraperitoneal injection was 1.87 (1.26-2.76)g/kg in male and female rats and 1.62 (1.18-2.24)g/kg in male and female mice, respectively. The LD50 after oral administration was over 8 g/kg in both sexes of rat and mice. PMID: 8924901 [PubMed - indexed for MEDLINE] 14: Planta Med. 1995 Aug;61(4):358-60. Related Articles, Links Characterization of the hypoglycemic effects of Trigonella foenum graecum seed. Ali L, Azad Khan AK, Hassan Z, Mosihuzzaman M, Nahar N, Nasreen T, Nur-e-Alam M, Rokeya B. The whole powder of Trigonella foenum graecum seeds and its extracts were tested for their hypoglycemic effect on normal and diabetic model rats. The powder, its methanol extract, and the residue remaining after methanol extraction had significant hypoglycemic effects when fed simultaneously with glucose. The water extract of the methanol extractive-free residue of the seed powder showed significant hypoglycemic activity at different prandial states. The Soluble Dietary Fibre (SDF) fraction showed no effect on the fasting blood glucose levels of nondiabetic or NIDDM model rats. However, when fed simultaneously with glucose, it showed a significant hypoglycemic effect (p < 0.05) in NIDDM model rats. Chemical analysis showed that the major constituent of the SDF is a galactomannan. The results confirm the involvement of SDF in the hypoglycemic effect of T. foenum graecum seeds. However, compound(s) other than SDF is (are) also involved in the hypoglycemic activity. Publication Types: Letter PMID: 7480183 [PubMed - indexed for MEDLINE] 15: Acta Pharmacol Sin. 2003 Jan;24(1):50-4. Hypoglycemic activity of ginseng glycopeptide. Related Articles, Links Wang BX, Zhou QL, Yang M, Wang Y, Cui ZY, Liu YQ, Ikejima T. Jilin Institute of Natural Medicine, Jilin University, Changchun 130021, China. cctcmwbx@public.cc.jl.cn AIM: To study the hypoglycemic activity of ginseng glycopeptide (GGP). METHODS: Normal mice or rabbits and alloxan or streptozotocin-induced hyperglycemic rats or mice were used in the study. Blood glucose and liver glycogen levels of the experimental animals during the trial period were analyzed by spectrophotometry with O-toluidine and iodine reagents, respectively. RESULTS: Significant decreases in blood glucose and liver glycogen levels were induced in a dose-dependent manner after administration of GGP 50, 100, or 200 mg/kg injected ip or sc to normal mice and injected im 30 or 60 mg/kg to normal rabbits. The hypoglycemic activity of GGP lasted for about 16 h, and were examined in both normal animals and hyperglycemic animals. CONCLUSION: GGP injection induced the pronounced decreases in blood glucose and liver glycogen levels in both normal and hyperglycemic animals. PMID: 12511229 [PubMed - indexed for MEDLINE] 16: Phytother Res. 2001 Mar;15(2):157-61. Related Articles, Links Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models. Okyar A, Can A, Akev N, Baktir G, Sutlupinar N. Department of Pharmacology, Faculty of Pharmacy, University of Istanbul, 34452 Universite, Istanbul, Turkey. Aloe vera (L.) Burm. fil. (= A. barbadensis Miller) (Liliaceae) is native to North Africa and also cultivated in Turkey. Aloes have long been used all over the world for their various medicinal properties. In the past 15 years, there have been controversial reports on the hypoglycaemic activity of Aloe species, probably due to differences in the parts of the plant used or to the model of diabetes chosen. In this study, separate experiments on three main groups of rats, namely, nondiabetic (ND), type I (IDDM) and type II (NIDDM) diabetic rats were carried out. A. vera leaf pulp and gel extracts were ineffective on lowering the blood sugar level of ND rats. A. vera leaf pulp extract showed hypoglycaemic activity on IDDM and NIDDM rats, the effectiveness being enhanced for type II diabetes in comparison with glibenclamide. On the contrary, A. vera leaf gel extract showed hyperglycaemic activity on NIDDM rats. It may therefore be concluded that the pulps of Aloe vera leaves devoid of the gel could be useful in the treatment of non-insulin dependent diabetes mellitus Copyright 2001 John Wiley & Sons, Ltd. PMID: 11268118 [PubMed - indexed for MEDLINE] 17: J Ethnopharmacol. 2001 Aug;76(3):269-77. Related Articles, Links Effect of an antidiabetic extract of Catharanthus roseus on enzymic activities in streptozotocin induced diabetic rats. Singh SN, Vats P, Suri S, Shyam R, Kumria MM, Ranganathan S, Sridharan K. Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi 110054, India. shoba72@yahoo.com Hypoglycemic activity was detected in dichloromethane:methanol extract (1:1) of leaves and twigs of Catharanthus roseus (family Apocynaceae), a traditionally used medicinal plant, using streptozotocin (STZ) induced diabetic rat model. Extract at dose 500 mg/kg given orally for 7 and 15 days showed 48.6 and 57.6% hypoglycemic activity, respectively. Prior treatment at the same dose for 30 days provided complete protection against STZ challenge (75 mg/kg/i.p.x1). Enzymic activities of glycogen synthase, glucose 6-phosphate-dehydrogenase, succinate dehydrogenase and malate dehydrogenase were decreased in liver of diabetic animals in comparison to normal and were significantly improved after treatment with extract at dose 500 mg/kg p.o. for 7 days. Results indicate increased metabolization of glucose in treated rats. Increased levels of lipid peroxidation measured as 2-thiobarbituric acid reactive substances (TBARS) indicative of oxidative stress in diabetic rats were also normalized by treatment with the extract. PMID: 11448549 [PubMed - indexed for MEDLINE] 18: Therapie. 2001 Jul-Aug;56(4):427-30. Related Articles, Links Preliminary evaluation of the hypoglycemic effect of some Brazilian medicinal plants. Novaes AP, Rossi C, Poffo C, Pretti Junior E, Oliveira AE, Schlemper V, Niero R, CechinelFilho V, Burger C. Nucleo de Investigacoes Quimico-Farmaceuticas (NIQFAR), Centro de Ensino Superior em Ciencias da Saude (CCS), Universidade do Vale do Itajai, UNIVALI, Rua Uruguai 458, 88302202, Itajai, SC, Brazil. The hypoglycemic effect of five Brazilian medicinal plants (Epidendrum monsenii, Marrubium vulgare, Rheedia gardneriana, Rubus imperialis and Wedelia paludosa) was studied on alloxaninduced diabetic rats. The extract of these plants was intragastrically administered to diabetic rats. The results showed that all plants studied (except R. gardneriana) significantly lowered the blood glucose. These results suggest that these four medicinal plants could be an adjuvant agent in the treatment of diabetes mellitus. PMID: 11677867 [PubMed - indexed for MEDLINE] 19: Indian J Physiol Pharmacol. 1983 Jul-Sep;27(3):257-8. Related Articles, Links Hypoglycaemic activity of an indigenous drug (Gymnema sylvestre, 'Gurmar') in normal and diabetic persons. Khare AK, Tondon RN, Tewari JP. Publication Types: Letter PMID: 6668058 [PubMed - indexed for MEDLINE] 20: J Ethnopharmacol. 1999 Nov 30;67(3):367-72. Related Articles, Links A comparative evaluation of some blood sugar lowering agents of plant origin. Chattopadhyay RR. Biometry Research Unit, Indian Statistical Institute, Calcutta. A comparison of blood sugar lowering activity of four important medicinal plants (Azadirachta indica, Gymnema sylvestre, Catharanthus roseus and Ocimum sanctum) were carried out against normal and streptozotocin-induced diabetic rat models. The plant extracts decreased the blood sugar level in varying degrees. Blood sugar lowering unit (BLU) of activity of each leaf extract and tolbutamide was calculated by ED50 values. Statistical analysis revealed significant (P < 0.05) variation among the treatments as well as doses with regard to their blood sugar lowering capacity. A. indica leaf extract was found to have the most potent blood sugar-lowering activity followed by C. roseus, G. sylvestre and O. sanctum. PMID: 10617074 [PubMed - indexed for MEDLINE] 21: J Ethnopharmacol. 2003 Jan;84(1):105-8. Related Articles, Links Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic rats. Kar A, Choudhary BK, Bandyopadhyay NG. Satsang Herbal Research and Analytical Laboratories, PO Satsang-814 116 Deoghar, India. pratip_neogy@hotmail.com In our experiments 30 hypoglycaemic medicinal plants (known and less known) have been selected for thorough studies from indigenous folk medicines, Ayurvedic, Unani and Siddha systems of medicines. In all the experiments with different herbal samples (vacuum dried 95% ethanolic extracts), definite blood glucose lowering effect within 2 weeks have been confirmed in alloxan diabetic albino rats. Blood glucose values are brought down close to normal fasting level using herbal samples at a dose of 250 mg/kg once, twice or thrice daily, as needed. While evaluating comparative hypoglycaemic activity of the experimental herbal samples, significant blood glucose lowering activities are observed in decreasing order in the following 24 samplesCoccinia indica, Tragia involucrata, G. sylvestre, Pterocarpus marsupium, T. foenum-graecum, Moringa oleifera, Eugenia jambolana, Tinospora cordifolia, Swertia chirayita, Momordica charantia, Ficus glomerata, Ficus benghalensis, Vinca rosea, Premna integrifolia, Mucuna prurita, Terminalia bellirica, Sesbenia aegyptiaca, Azadirachta indica, Dendrocalamus hamiltonii, Zingiber officinale, Aegle marmelos, Cinnamomum tamala, Trichosanthes cucumerina and Ocimum sanctum. Present studies besides confirming hypoglycaemic activities of the experimental herbal samples, help identify more potent indigenous hypoglycaemic herbs (in crude ethanolic extract) from the comparative study of the reported experimental results. Copyright 2002 Published by Elsevier Science Ireland Ltd. PMID: 12499084 [PubMed - indexed for MEDLINE] 22: Altern Med Rev. 1999 Feb;4(1):46-7. Related Articles, Links Gymnema sylvestre. [No authors listed] PMID: 9988783 [PubMed - indexed for MEDLINE] 23: Arch Med Res. 1992 Spring;23(1):59-64. Related Articles, Links Hypoglycemic effect of plants used in Mexico as antidiabetics. Roman Ramos R, Alarcon-Aguilar F, Lara-Lemus A, Flores-Saenz JL. Health Sciences Department, Biological and Health Sciences Division, Metropolitan Autonomous University, Iztapalapa Campus, Mexico City. The objective of this work is to investigate the hypoglycemic effect of 12 "antidiabetic" plants used in Mexico. The studies were performed using 27 healthy rabbits with the gastric administration of water, tolbutamide or decoction of the "antidiabetic" plant before the induction of temporary hyperglycemia by subcutaneous injection of 50% dextrose solution (4 ml/kg of weight) at the beginning of the experiment and after 60 min. Blood glucose was determined every 60 min for a period of 5 h. Tolbutamide and eight of the studied plants decreased significantly the hyperglycemia as compared with control test (water) (p < 0.05). The strongest effect was yielded by Guaiacum coulteri, followed by Marrubium vulgare, Crataegus pubescens, Cynodon dactylon, Calea zacatechichi, Buddleia americana, Bauhinia divaricata and Coix lachryma. The decrease of hyperglycemia caused by Physalis phyladelphyca, Pavonia schiedeana and Eucaliptus globulus was not significant (p > 0.05). Urtica dioica increased glycemia slightly. PMID: 1308793 [PubMed - indexed for MEDLINE] 24: Pharmacol Res Commun. 1981 May;13(5):475-86. Related Articles, Links The insulinotropic activity of Gymnema sylvestre, R. Br. An Indian medical herb used in controlling diabetes mellitus. Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER. PMID: 7027275 [PubMed - indexed for MEDLINE] 25: Chem Pharm Bull (Tokyo). 1996 Feb;44(2):469-71. Related Articles, Links New hypoglycemic constituents in "gymnemic acid" from Gymnema sylvestre. Murakami N, Murakami T, Kadoya M, Matsuda H, Yamahara J, Yoshikawa M. Kyoto Pharmaceutical University, Japan. Investigation of hypoglycemic activity of major saponin constituents from "gymnemic acid", a crude saponin fraction of G. sylvestre, exposed not only two new saponins, gymnemosides a (1) and b (2), but also gymnemoside b and gymnemic acid V (7) as active principles. Furthermore, an acetyl group linked 16- or 22-hydroxy group in 1 and 2 was found to migrate easily to primary 28hydroxyl group, while acyl migration from 28-hydroxy group in 3 was little observed. PMID: 8998848 [PubMed - indexed for MEDLINE] 26: Zhong Yao Cai. 2003 Apr;26(4):305-7. Related Articles, Links [Advances in the study on hypoglycemic constituents of Gymnema sylvestre (Retz.) Schult] [Article in Chinese] Jiang H. Guangxi College of Traditional Chinese Medicine, Nanning, Guangxi Province, 530001 Publication Types: Review Review, Tutorial PMID: 14631994 [PubMed - indexed for MEDLINE] 27: Exp Diabesity Res. 2003 Jul-Sep;4(3):183-9. Related Articles, Links Effect of Gymnema montanum leaves on serum and tissue lipids in alloxan diabetic rats. Ananthan R, Latha M, Ramkumar KM, Pari L, Baskar C, Narmatha Bai V. Department of Botany, Bharathiar University, Coimbatore, Tamil Nadu, India. botananthan@lycos.com The effect of Gymnema montanum leaves on alloxan-induced hyperlipidemia was studied in male Wistar rats. Ethanolic extract of G. montanum leaves was administered orally and different doses of the extract on blood glucose, serum and tissue lipids, hexokinase, glucose-6-phosphatase, thiobarbituric acid-reactive substances (TBARS), hydroperoxides, and glutathione in alloxaninduced diabetic rats were studied. G. montanum leaf extract (GLEt) at doses of 50, 100, 200 mg/kg body weight for 3 weeks suppressed the elevated blood glucose and lipid levels in diabetic rats. GLEt at 200 mg/kg body weight was found to be comparable to glibenclamide, a reference drug. These data indicate that G. montanum represents an effective antihyperglycemic and antihyperlipidemic adjunct for the treatment of diabetes and a potential source of discovery of new orally active agent for future therapy. PMID: 15061646 [PubMed - in process] 28: Pharmacol Res. 2003 Dec;48(6):551-6. Related Articles, Links Antidiabetic effect of Gymnema montanum leaves: effect on lipid peroxidation induced oxidative stress in experimental diabetes. Ananthan R, Baskar C, NarmathaBai V, Pari L, Latha M, Ramkumar KM. Department of Botany, Bharathiar University, Coimbatore 641046, Tamil Nadu, India. botananthan@lycos.com Gymnema montanum is widely used in ancient medicine for the ailment of various diseases. Oral administration of 200 mg kg(-1) (body weight) BW of the alcoholic extract of the leaf for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin, whereas the effect of 50 and 100 mg kg(-1) BW was not significant. The alcoholic extract also resulted in decreased free radical formation in plasma of diabetic rats. Thus, this study shows that Gymnema montanum leaf extract (GLEt) possess antihyperglycemic and antiperoxidative effect. The decrease in lipid peroxides and increase in reduced glutathione (GSH), ascorbic acid (Vitamin C) and alpha-tocopherol (Vitamin E) clearly show the antioxidant properties of GLEt. The effect of GLEt was most prominently seen in the case of animals given 200 mg kg(-1) BW. In addition, the results suggest that GLEt was highly effective than the reference drug glibenclamide. PMID: 14527818 [PubMed - in process] 29: J Ethnopharmacol. 1984 Jul;11(2):223-31. Related Articles, Links Oral hypoglycaemic activity of some medicinal plants of Sri Lanka. Karunanayake EH, Welihinda J, Sirimanne SR, Sinnadorai G. Investigations were carried out to evaluate the oral hypoglycaemic activity of some Sri Lankan medicinal plants. Approximately 40 plants available locally are reputed to have oral hypoglycaemic activity. Of these, the mostly widely used are (a) Salacia reticulata (Celastraceae) (b) Aegle marmelos (Rutaceae) and (c) Momordica charantia (Cucurbitaceae). Aqueous decoctions of these plants were investigated for their ability to lower the fasting blood glucose level and improve the glucose tolerance in laboratory animals. The results indicate that the aqueous decoctions of all three plants possess significant hypoglycaemic effect. The magnitude of this effect showed time related variation with the three plants. The highest oral hypoglycaemic activity and the maximum improvement of the oral glucose tolerance were associated with the extract of Momordica charantia while the least but significant effects were shown by Salacia reticulata. PMID: 6492834 [PubMed - indexed for MEDLINE] 30: J Ethnopharmacol. 1995 Jun 23;47(1):9-26. Related Articles, Links Plant-derived triterpenoid sweetness inhibitors. Suttisri R, Lee IS, Kinghorn AD. Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612, USA. Considerable recent attention has been focused on naturally occurring compounds with tastemodifying activity, which are of potential use in both dietary sweetness management and in gaining a better understanding of the sweet taste sensation. This review summarizes information on the phytochemistry and biological activity of more than 40 triterpenoid sweetness inhibitors that have been isolated from the leaves of three medicinal plants, namely, Gymnema sylvestre R.Br. (Asclepiadaceae), Ziziphus jujuba P. Miller (Rhamnaceae), and Hovenia dulcis Thunb. (Rhamnaceae). Publication Types: Review Review, Tutorial PMID: 7564423 [PubMed - indexed for MEDLINE] 31: Biochem Soc Trans. 1979 Feb;7(1):99-102. Related Articles, Links An introduction to the control of carbohydrate metabolism: possible sites for pharmacological intervention in hyperglycaemia. Sherratt HS, Hue L. PMID: 437303 [PubMed - indexed for MEDLINE] 32: J Pharm Sci. 1967 Jun;56(6):732-6. Related Articles, Links Constituents from Gymnema sylvestre leaves. II. Nitrogenous compounds. Sinsheimer JE, McIlhenny HM. PMID: 6039815 [PubMed - indexed for MEDLINE] 33: J Pharm Sci. 1965 Oct;54(10):1541-4. Related Articles, Links Constituents from Gymnema sylvestre leaves. Manni PE, Sinsheimer JE. PMID: 5883239 [PubMed - indexed for MEDLINE] 34: J Med Food. 2003 Spring;6(1):43-9. Related Articles, Links Effect of Gymnema montanum on blood glucose, plasma insulin, and carbohydrate metabolic enzymes in alloxan-induced diabetic rats. Ananthan R, Latha M, Pari L, Ramkumar KM, Baskar CG, Bai VN. Department of Botany, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India. The effects of Gymnema montanum, an endangered plant used in the ancient period of India, on blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in alloxan diabetic rats. Administration of alcoholic extract of G. montanum leaves (50, 100, 200 mg/kg body weight) to alloxan diabetic rats for 3 weeks reduced the blood glucose level. Administration of G. montanum leaf extract (GLEt) at 200 mg/kg body weight significantly decreased the blood glucose levels and significantly increased the plasma insulin levels. This clearly shows the antidiabetic efficacy of GLEt, which was better than that of glibenclamide. PMID: 12804019 [PubMed - indexed for MEDLINE] 35: J Ethnopharmacol. 1983 Mar;7(2):205-34. Related Articles, Links Enzyme changes and glucose utilisation in diabetic rabbits: the effect of Gymnema sylvestre, R.Br. Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER. The administration of the dried leaf powder of Gymnema sylvestre regulates the blood sugar levels in alloxan diabetic rabbits. G. sylvestre therapy not only produced blood glucose homeostasis but also increased the activities of the enzymes affording the utilisation of glucose by insulin dependent pathways: it controlled phosphorylase levels, gluconeogenic enzymes and sorbitol dehydrogenase. The uptake and incorporation of [14C] glucose into the glycogen and protein are increased in the liver, kidney and muscle in G. sylvestre administered diabetic animals when compared to the untreated diabetic animals. Pathological changes initiated in the liver during the hyperglycemic phase are reversed by controlling hyperglycemia by G. sylvestre. G. sylvestre, a herb used for the control of diabetes mellitus in several parts of India, appears to correct the metabolic derangements in diabetic rabbit liver, kidney and muscle. PMID: 6865451 [PubMed - indexed for MEDLINE] 36: Therapie. 2001 Jul-Aug;56(4):427-30. Related Articles, Links Preliminary evaluation of the hypoglycemic effect of some Brazilian medicinal plants. Novaes AP, Rossi C, Poffo C, Pretti Junior E, Oliveira AE, Schlemper V, Niero R, CechinelFilho V, Burger C. Nucleo de Investigacoes Quimico-Farmaceuticas (NIQFAR), Centro de Ensino Superior em Ciencias da Saude (CCS), Universidade do Vale do Itajai, UNIVALI, Rua Uruguai 458, 88302202, Itajai, SC, Brazil. The hypoglycemic effect of five Brazilian medicinal plants (Epidendrum monsenii, Marrubium vulgare, Rheedia gardneriana, Rubus imperialis and Wedelia paludosa) was studied on alloxaninduced diabetic rats. The extract of these plants was intragastrically administered to diabetic rats. The results showed that all plants studied (except R. gardneriana) significantly lowered the blood glucose. These results suggest that these four medicinal plants could be an adjuvant agent in the treatment of diabetes mellitus. PMID: 11677867 [PubMed - indexed for MEDLINE] 37: Indian J Physiol Pharmacol. 1983 Jul-Sep;27(3):257-8. Related Articles, Links Hypoglycaemic activity of an indigenous drug (Gymnema sylvestre, 'Gurmar') in normal and diabetic persons. Khare AK, Tondon RN, Tewari JP. Publication Types: Letter PMID: 6668058 [PubMed - indexed for MEDLINE] 38: J Ethnopharmacol. 1999 Nov 30;67(3):367-72. Related Articles, Links A comparative evaluation of some blood sugar lowering agents of plant origin. Chattopadhyay RR. Biometry Research Unit, Indian Statistical Institute, Calcutta. A comparison of blood sugar lowering activity of four important medicinal plants (Azadirachta indica, Gymnema sylvestre, Catharanthus roseus and Ocimum sanctum) were carried out against normal and streptozotocin-induced diabetic rat models. The plant extracts decreased the blood sugar level in varying degrees. Blood sugar lowering unit (BLU) of activity of each leaf extract and tolbutamide was calculated by ED50 values. Statistical analysis revealed significant (P < 0.05) variation among the treatments as well as doses with regard to their blood sugar lowering capacity. A. indica leaf extract was found to have the most potent blood sugar-lowering activity followed by C. roseus, G. sylvestre and O. sanctum. PMID: 10617074 [PubMed - indexed for MEDLINE] 39: J Ethnopharmacol. 2003 Jan;84(1):105-8. Related Articles, Links Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic rats. Kar A, Choudhary BK, Bandyopadhyay NG. Satsang Herbal Research and Analytical Laboratories, PO Satsang-814 116 Deoghar, India. pratip_neogy@hotmail.com In our experiments 30 hypoglycaemic medicinal plants (known and less known) have been selected for thorough studies from indigenous folk medicines, Ayurvedic, Unani and Siddha systems of medicines. In all the experiments with different herbal samples (vacuum dried 95% ethanolic extracts), definite blood glucose lowering effect within 2 weeks have been confirmed in alloxan diabetic albino rats. Blood glucose values are brought down close to normal fasting level using herbal samples at a dose of 250 mg/kg once, twice or thrice daily, as needed. While evaluating comparative hypoglycaemic activity of the experimental herbal samples, significant blood glucose lowering activities are observed in decreasing order in the following 24 samples- Coccinia indica, Tragia involucrata, G. sylvestre, Pterocarpus marsupium, T. foenum-graecum, Moringa oleifera, Eugenia jambolana, Tinospora cordifolia, Swertia chirayita, Momordica charantia, Ficus glomerata, Ficus benghalensis, Vinca rosea, Premna integrifolia, Mucuna prurita, Terminalia bellirica, Sesbenia aegyptiaca, Azadirachta indica, Dendrocalamus hamiltonii, Zingiber officinale, Aegle marmelos, Cinnamomum tamala, Trichosanthes cucumerina and Ocimum sanctum. Present studies besides confirming hypoglycaemic activities of the experimental herbal samples, help identify more potent indigenous hypoglycaemic herbs (in crude ethanolic extract) from the comparative study of the reported experimental results. Copyright 2002 Published by Elsevier Science Ireland Ltd. PMID: 12499084 [PubMed - indexed for MEDLINE] 1: J Pak Med Assoc. 1988 Nov;38(11):289-95. Related Articles, Links Effect of Grewia asiatica, Gossypium herbacium and Gymnema sylvestre on blood glucose, cholesterol and triglycerides levels in normoglycaemic and alloxan diabetic rabbits. Dogar IA, Ali M, Yaqub M. PMID: 3148751 [PubMed - indexed for MEDLINE] 2: Diabetes Res Clin Pract. 1995 Jul;29(1):11-7. Related Articles, Links Effects of seishin-renshi-in and Gymnema sylvestre on insulin resistance in streptozotocininduced diabetic rats. Tominaga M, Kimura M, Sugiyama K, Abe T, Igarashi K, Igarashi M, Eguchi H, Sekikawa A, Ogawa A, Manaka H, et al. Third Department of Internal Medicine, Yamagata University School of Medicine, Japan. Although there is no concept of insulin resistance in traditional Kampo (Chinese) medicine and Indian medicine, we had the hypothesis that some drug in a mixture of crude drugs which was believed to ameliorate diabetes mellitus may have had the effect of improving insulin resistance. To test this hypothesis, the effects of Seishin-renshi-in (Chinese medicine) and Gymnema sylvestre (Indian medicine) on the insulin resistance of streptozotocin-induced diabetic rats was studied by the glucose clamp technique. Oral administration of Seishin-renshi-in (800 mg/kg/day) with injections of a minimum dose of Ultralente insulin decreased urine volume and urinary glucose excretion during a 7-day treatment period and improved the insulin stimulated glucose uptake in peripheral tissues, as well as improving the insulin suppressed hepatic glucose output during glucose clamp. However, G. sylvestre (120 mg/kg/day) treatment did not improve insulin resistance. We conclude that Seishin-renshi-in, with a small dose of insulin, improved insulin resistance in streptozotocin-induced diabetic rats, but Gymnema sylvestre did not. PMID: 8593754 [PubMed - indexed for MEDLINE] 3: Comp Biochem Physiol A. 1972 Oct 1;43(2):381-91. Related Articles, Links Comparative electrocardiography in lizards: effects of temperature and Gymnema sylvestre fractions. Yackzan KS, Yousef MK, Dill DB. PMID: 4145248 [PubMed - indexed for MEDLINE] 4: Bull Calcutta Sch Trop Med. 1966 Oct;14(4):126-7. Crystalline saponin from Gymnema sylvestre. Chakravarti RN, Chakravarti D, Itty MI. PMID: 6003983 [PubMed - indexed for MEDLINE] Related Articles, Links