effect of intravenous oxytocin injections on plasma levels

54 (4) 1999
N. Sulu1, M. Uzun2, T. Sel3 and A. ַynar4
1. University of Ankara, Faculty of Veterinary Medicine, Department of Physiology, 06110 Dyskapy, Ankara
2. University of Kafkas, Faculty of Veterinary Medicine, Department of Physiology, Kars
3. University of Ankara, , Faculty of Veterinary Medicine, Department of Biochemstry, 06110, Dyskapy, Ankara
rinary Medicine, Department of Physiology, Kampus, Van Turkey
The effect of intravenous injection of oxytocin on plasma insulin and glucose levels in dairy cows
was investigated. Experiments were performed on 3 years old, nonpregnant Holstein cows. In this
study cows were allocated in four groups, each consisting of four cows. One group was chosen as
a control.
Isotonic NaCl was administrated by infusion during 30 minutes in the control group. In the first
group 1.8 mU/kg/min., in the second group 3.6 mU/kg/min., and in the third group 5.4 mU/kg/min.
oxytocin was given by infusion in 0.5 NaCl during 30 minutes. All infusions were given into the
jugular vein.
Blood samples were collected and examined for insulin and glucose measurement at time 0, and at
12, 24, 36 and 48 minutes. Glucose concentrations were determined by glucose - oxidase method
and plasma insulin by RIA.Insulin levels were increased in the second and third groups at 12
minutes to 62 % and 16 % respectively. Glucose levels remained unchanged during the
experimental period.
Oxytocin is a nonapeptide hormone synthesized in the supraoptic and
paraventricular nuclei of the hypothalamus (19). Oxytocin affects uterine
smooth muscle contraction during parturition and mammary gland muscles
during milk ejection. In addition its receptors are present in the oviduct, and
the hormone is released during mating of female goats. It has an effect on the
blood pressure (5,18,24). It is believed that oxytocin has some affect on the
central nervous system such as memory, learning capability, nursing, sexual
and feeding behaviour (3,20). In addition researchers have examined its effects
on insulin, glucagon and glucose blood levels. Oxytocin increases their levels
in rabbits and dogs (2,16,25). Additionally, oxytocin affects the release of
insulin and glucagon during and after birth in sheep (26). The insulin tolerance
test (ITT) shows that overweight people release less oxytocin than ones with
normal weight (8,9). Insulin also effects oxytocin and vasopressin release in
man (10). Oxytocin and vasopressin stimulate the release of insulin and
glucagon from the rat pancreas. The pancreatic binding sites for oxytocin are
localized in the islets of Langerhans, and more precisely, in the periphery of
the islets (22).
Some workers have shown that infusion of oxytocin causes a rise in plasma
glucagon which is accompanied by elevated plasma insulin levels in the dog
(2,25). It was found that insulin levels rise before glucagon and glucose levels
increase (21).
Digestable carbohydrates in the ruminant stomach are converted to free fatty
acids by bacteria and are then absorbed. Body glucose requirements are
provided by gluconeogenesis from glucogenic precursors such as propionate
and amino acids. Available glucose
metabolism is under hormonal control (15).
Glucose metabolism is very important for a variety of organs and tissues such
as nerves, retina, germinative epithelium and heart and it is closely related to
milk lactose, and is directly dependant on growth hormone and blood insulin
levels (7). During lactation, the blood levels of insulin, glucagon, growth
hormone and glucose can rary. Growth hormone levels decrease, while insulin
levels increase whereas glucagon levels do not change considerably. Blood
glucose levels increase until the 200th day of lactation (14).
In dairy cows plasma insulin levels change during the day after feeding, while
such changes are minumal during the night. Plasma glucose levels do not alter.
This can be explained by the finding that feeding stimulates the release of
insulin which facilitates the transport of glucose into the cells, thereby
reducing the concentration of blood glucose (15). In bulls, plasma insulin
levels also increase after feeding. Bulls have higher plasma glucose levels than
cows because of utilizing the carbohydrate stocks (6). Differences in energy
metabolism also show that blood glucose levels decrease with rumenal
development in calves (23,26).
The aim of the present study was to investigate the effects of oxytocin on
monogastric animals and on dairy cows which have less blood glucose
compared to calves and lambs and to compare these findings with other animal
Materials and Methods
Animals: The experiment was performed on sixteen, three years old,
nonpregnant Holstein dairy cows. The cows were fed and watered four hours
prior to receiving oxytocin. During the infusion of oxytocin they were not fed
or watered.
Application of oxytocin: Four groups of 4 were made. One group was chosen
as the control. Isotonic NaCl was administrated into the control group by
infusion for 30 minutes. In the first group, 1.8 mU/kg/min, in the second group
3.6 mU/kg/min, and in the third group 5.4 mU/kg/min of oxytocin was given
by infusion with 0.5 l. isotonic NaCl in 30 min. All infusions were made into
the jugular vein.
Blood samples were taken from the jugular vein with polyethylene catheters.
In order not to stress the animals when blood was taken from one vein,
infusion was performed into the other vein. Blood samples collected before
hormone application were considered as Time 0. Subsequently, blood samples
were taken at 12, 24, 36 and 48 minutes. With this method while the oxytocin
application continuing two after the application 2 more blood samples were
taken. These blood samples were placed in heparinized tubes, and were
immediately centrifuged at 4 C and the plasma removed. Glucose analysis was
done right away but insulin analysis was performed on plasma that had been
stored at –20 C.
Analyses of samples: Glucose concentration was determined by glucoseoxidase method using a Sigma diagnostic glucose kit (Cat. No: 315-100). For
plasma insulin levels, DPC company’s radioimmunoassay kit (Cat.TK / N1)
was used (23).
Statistical analysis: Values compared by ANOVA and nonpaired t tests.
The plasma concentrations of insulin and glucose for control and experimental groups are given in
Table 1 - 4.
The effects of vasopressin and oxytocin in animals are well known, but
recently, researchers has been trying to learn more on the effects of these
hormones on energy metabolism. Knudtzon observed that the levels of insulin
and glucose in rabbits were increased after giving oxytocin and vasopressin
In mice, oxytocin stimulates inositol phosphate metabolism, affects the
pancreas directly and starts the release of insulin. (4,11). When the oxytocin
was applied to islets of Langerhans in the isolated mouse pancreas, it caused
release of insulin and glucagon (12,13). This experiment shows that oxytocin
directly affects the pancreas. When oxytocin was applied to pancreas locally,
it increased insulin levels by 210% and glucagon level by 528% in the rat
The results of this investigation showed that glucose level was the same during
the experiment, for the control, second and third groups (Tables 1, 3 and 4). In
contrast, in first group the glucose level dropped at 12 minutes but this change
was not statistically significant (Table 2). We believed that the effect of
oxytocin on blood glucose level does not depend on dosage. The results of the
control group in this study were similiar to those of Herbein et al(14) .
Although Knudtzon applied 0.3 µg oxytocin the glucose level did not change
significantly in the rabbit (16).
Finally, even though glucose requirements in cows are much less than in other
species, the effect of oxytocin application in rabbits, dogs, lambs and humans
is the same as in the cow. The only difference is that this effect always
remained in limit and was dependent on the dosage. From these results and
with the results of location of insulin receptors in the rat and mouse pancreatic
( cells and the direct application to pancreas leads us to investigate the
oxytocin receptor in vivo and in vitro.
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