— Chapter 7 The Pancreatic Islets focusing on insulin

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Chapter 7—
The Pancreatic Islets
focusing on insulin
7-1
Ch. 7-- Study Guide
1. Critically read (1) pages pp. 129-130 before
Glucagon section; skip Glucagon section
(pp. 130-134); (2) pages 134-143 (Insulin
section) before Mechanism of insulin action
subsection; skip Mechanism of insulin action
subsection (p. 143). (3) pages 144-146
before Hormonal and neural control
subsection
2. Comprehend Terminology (the text in
bold/italic)
3. Study and understand the text and
corresponding figures.
7-2
7.1. Introduction—
Where is the pancreas?
7-3
The pancreas
7-4
§ Introduction
1. Principal pancreatic hormones: insulin and
glucagon (both are _____ hormones)
2. Function of the insulin– an anabolic
hormone that promotes CHO, fat, and protein
storage
3. (Locations) Insulin’s target organs– skeletal
muscle, liver, and adipose tissue
4. Diseases–
A. Diabetes mellitus type I– insufficient production
B. Diabetes mellitus type II—decreased end organ
sensitivity to insulin
7-5
7.2. Morphology of the
endocrine pancreas
7-6
§ The pancreas and islets
1. Islets makes up about 2% of the pancreas
2. Blood circulation– by the pancreatic artery
and drains into the portal vein toward the liver
3. The islets--highly vascular and each cell
seems in directly contact with a capillary
4. (Nerve) The islets are innervated richly with
sympathetic and parasympathetic fibers
5. Histology—Three major cell types: Fig. 7.1 + x
1. Beta cells (60% of the islet)– produce insulin
2. Alpha cells (30% of the islet)– produce glucagon
3. Delta cells (the least)—produce somatostatin 7-7
A typical human pancreatic islet
7-8
Pancreas
7-9
7.3. Insulin—Biosynthesis,
secretion, and metabolism
7-10
§ Biosynthesis and metabolism
1. Biosynthesis and secretion [in _____ cells of
the ________ (what organ)]: Fig. 7.8
A. (At ER) Preproinsulin becomes proinsulin– by
cutting of the leader sequence; forming single
chain proinsulin and disulfide bond formation
B. (at Golgi) packaging
C. (Forming mature insulin in granules)–
converting into insulin (two chains) by cutting
away the C (connecting) peptide
2. Metabolism (mainly in the liver)– half-life
about 5 minutes; using receptor-mediated
endosomic mechanism; also in kidneys, muscle,
and others
7-11
(110 amino acids)
A--at E. R.
B-Golgi
(51 a.a.)
(31 a.a.)
(110 amino acids)
C--in secretory granules
7-12
7.4. Insulin—Physiological
actions of insulin:
A. Effects of
insulin deficiency
7-13
§ signs of insulin deficiency (A)
1. Hyperglycemia– normal individuals (90
mg/dL of plasma); in diabetics: 300 to 400
mg/dL; testing diabetics by oral glucose
tolerance tests (Fig. 7.9)
2. Glycosuria– excretion of glucose in urine;
this is due to too much ___ in the blood &
renal filtrate
3. Polyphagia/Polydipsia/Polyuria–
– Excessive food consumption— due to increased in
appetite to compensate for urinary lose of glucose
– Excessive drinking– due to dehydration
– Excessive urine– due to increased glucose in renal
7-14
filtrate
7-15
§ signs of insulin deficiency (B)
4. Weight loss–
A. Underutilization of glucose by muscle/adipose
tissue and overproduction of glucose by liver.
These phenomena lead to hyperglycemia and
items below.
B. due to reduced anabolic processes and increased
catabolic processes – severe reduction in the ability to
store glycogen, fat, and protein– marked wasting of
muscle with depletion of body fat stores
C. This leads to lipemia (high lipid conc. In blood)
D. Increased fatty acids oxidation by the liver resulting in
increased production of the ketone bodies (ketosis);
plasma pH may become too low (acidotic coma and death
possible)
7-16
§ Insulin’s effects
1. Target organs– adipose tissue, skeletal
muscle, and liver
2. Physiology–
1. on above organs to defend and expand reserves
of triglyceride, glycogen, and protein
2. Lower plasma glucose conc., amino acids,
FFA etc. (If blood glucose too low –
hypoglycemic coma)
3. How? (A) insulin increases glucose uptake by
muscle and adipose tissue; (B) insulin decreases
glucose output by liver; (C) by stimulating a.a.
uptake by muscle; (D) by blocking FFA release
from adipocytes
7-17
Regulation
of glucose
metabolism
7-18
7.4. Insulin—Physiological
actions of insulin:
B. Effects on adipose tissue
7-19
§ Insulin on adipose tissue
1. Transport of glucose into
adipocytes– via glucose transporters
(GLUTs)
2. Accelerating glucose oxidation–
increase availability of glycerol phosphate
3. Promoting FAA uptake from the
lipoproteins of blood
4. Stimulating synthesis of
triglycerides
Fig. 7.10, 7.11, X
7-20
Reactions enhanced by insulin (green arrows) are 15. Reactions inhibited by insulin (dashed red arrows).
In adipocyte
7-21
A
B
In adipocyte
Confocal fluorescent microscope images of
cultured mouse adipocytes that were transfected
with GLUT4 linked to green fluorescent protein
and then incubated in the absence (A) or
presence (B) of insulin for 30 min.
7-22
(GLUT)
7-23
7.4. Insulin—Physiological
actions of insulin:
C. Effects on muscle
7-24
§ Insulin on muscle
1. Promotes glucose transport into
muscle– via glucose transporters (GLUTs);
similar to that in adipocytes
2. Promotes glycogen storage–
3. Promotes protein synthesis
Fig. 7.12, 7.13
7-25
In muscle cell
7-26
In muscle
7-27
7.4. Insulin—Physiological
actions of insulin:
D. Effects on liver
7-28
§ Insulin on liver
1. Promotes glycogen storage and
reduces outflow of glucose –
– In general, liver takes up glucose when the
circulating conc. Is high and releases it when the
blood level is low.
– Movement of glucose is passive and depends on
the glucose transporter.
2. Promotes fatty acid and protein
synthesis
3. Substrates from myocytes and
adipocytes influence hepatic effects
Fig. 7.14
7-29
7-30
7.5. Insulin—Regulation of
insulin secretion
7-31
§ Regulation of insulin secretion
• Insulin secretion is greatest right after
eating – Fig. 7.20
• How does it work?
1. Coordination of insulin secretion with nutritional
state is via direct monitoring of metabolites,
hormones, and neural signals by beta cells.
2. Glucose– is the most important regulator of insulin
secretion; however, beta cells do not have specific
receptors for glucose!!!
3. Other metabolites– a.a. and fatty acids are
important stimuli for insulin secretion
7-32
7-33
7-34
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