1. Unit Fourteen: Endocrinology and Reproduction
Chapter 78: Insulin, Glucagon, and
Diabetes Mellitus
Guyton and Hall, Textbook of Medical Physiology, 12 edition

2. Physiologic Anatomy of the Pancreas
Fig Physiolgic anatomy of an islet of Langerhans in the pancreas

3. Physiologic Anatomy of the Pancreas
Composed of two major types of tissues, the acini,
which secrete digestive juices, and the islets of
Langerhans, which secrete insulin and glucagon
directly into the blood
Alpha cells of the islets-secrete glucagon
Beta cells-secrete insulin
Delta cells-secrete somatostatin

4. Insulin and Its Metabolic Effects
Insulin is a Hormone Associated with Energy
Abundance
Composed of two amino acid chains, MW 5808
Preproinsulin to a proinsulin to insulin
In the blood, it circulates as an unbound form
Half-life in circulation is about 6 minutes

5. Insulin and Its Metabolic Effects
Fig. 78.2

6. Insulin and Its Metabolic Effects
Activation of Target Cell Receptors by Insulin and the Resulting Cellular Effects
Fig. 78.3

7. Insulin and Its Metabolic Effects
Activation of Target Cell Receptors by Insulin and the Resulting Cellular Effects
Within seconds after insulin binds to its receptors, 80% of the cells increase their uptake of glucose (true of muscle and adipose cells but not the neurons of the brain)
Cell membrane becomes more permeable to many amino acids, potassium ions, and phosphate ions, causing increased transport of these substances into the cell

8. Insulin and Its Metabolic Effects
Activation of Target Cell Receptors by Insulin and the Resulting Cellular Effects
c. Slower effects occur during the next minutes to change the activity levels of many more intracellular metabolic enzymes
d. Much slower effects continue for hours and even several days; enzymatic functions and protein synthesis

9. Insulin and Its Metabolic Effects
Effect of Insulin on Cbh Metabolism
Promotes muscle glucose uptake and metabolism; if the muscle is not exercising, the glucose is stored as muscle glycogen
Promotes liver uptake, storage, an use of glucose
Insulin inactivates liver phosphorylase and prevents the splitting of glycogen into glucose
Insulin causes the enhanced uptake of glucose from the blood by liver cells; increases the activity of glucokinase

10. Insulin and Its Metabolic Effects
Effect of Insulin on Cbh Metabolism
Increases the activity of the enzymes that promote glycogen synthesis
Glucose is released from the liver between meals
1) Decreasing blood glucose causes the pancreas
to decrease insulin secretion
2) Lack of insulin reverses the effects of glycogen
storage
3) Lack of insulin activates the splitting of
glycogen into glucose; glucose phosphatase is
activated

11. Insulin and Its Metabolic Effects
Effect of Insulin on Cbh Metabolism
Insulin promotes the conversion of excess glucose into fatty acids and inhibits gluconeogenesis in the liver
In the brain most of the cells are permeable to glucose and can use glucose without the intermediation of insulin

12. Insulin and Its Metabolic Effects
Effect of Insulin on Fat Metabolism
Promotes fat synthesis and storage
Increases the transport of glucose into liver cells; after the liver glycogen concentration reaches 5-6%, the glucose becomes available to form fat (split to acetyl CoA from pyruvate to make fatty acids)
Excesses of citrate and isocitrate are formed when excess amounts of glucose are being used for energy—activate enzymes for the first steps of fatty acid synthesis

13. Insulin and Its Metabolic Effects
Effect of Insulin on Fat Metabolism
Promotes fat synthesis and storage
Most of the fatty acids are then synthesized within the liver and used to form triglycerides
Role of insulin in the storage of fat in the adipose cells
Insulin inhibits the action of hormone sensitive lipase
Promotes glucose transport through the membrane into the fat cells

14. Insulin and Its Metabolic Effects
Effect of Insulin on Fat Metabolism
Insulin deficiency causes lipolysis of storage fat and the release of fatty acids
Insulin deficiency increases plasma cholesterol and phospholipid concentrations
Excess usage of fats during insulin lack causes ketosis and acidosis

15. Insulin and Its Metabolic Effects
Effect of Insulin on Protein Metabolism
Insulin promotes protein synthesis and storage of amino acids
Stimulates the transport of many of the aa into cells
Increases the translation of mRNA
Increases the rate of transcription of selected DNA genetic sequences
Inhibits the catabolism of proteins
In the liver, insulin depresses the rate of gluconeogenesis

16. Insulin and Its Metabolic Effects
Effect of Insulin on Protein Metabolism
Insulin deficiency causes protein depletion and increased plasma amino acids
Insulin and growth hormone interact synergistically to promote growth

17. Insulin and Its Metabolic Effects
Effect of Insulin on Protein Metabolism
Fig Effect of GH, insulin, and GH plus insulin on growth in a depancreatized and hypophysectomized rat

18. Insulin and Its Metabolic Effects
Mechanisms of Insulin Secretion
Fig Basic mechanisms of glucose stimulation of insulin secretion
by beta cells of the pancreas

19. Insulin and Its Metabolic Effects
Control of Insulin Secretion
Increased blood glucose stimulates insulin secretion
Fig Increase in plasma insulin concentration after a sudden increase in
blood glucose to 2-3x the normal range

20. Insulin and Its Metabolic Effects
Control of Insulin Secretion
Feedback relation between blood glucose concentration and insulin secretion rate- a rise in blood glucose increases the secretion of insulin which in turn increases the transport of glucose into liver, muscle, and other cells
Other factors that stimulate insulin secretion-amino acids, GI hormones, other hormones, ANS

21. Insulin and Its Metabolic Effects
Control of Insulin Secretion
Fig Approximate insulin secretion at different plasma glucose levels

22. Glucagon and Its Functions
Effects on Glucose Metabolism
Causes glycogenolysis and increased blood glucose concentration
Glucagon activates adenyl cyclase in the hepatic cell membrane
Which causes the formation of cAMP
Which activates protein kinase regulator protein
Which activates protein kinase
Which activates phosphorylase b kinase
Which converts phosphorylase b to a
Which promotes the degradation of glycogen into glucose-1-phosphate
Which is dephosphorylated and glucose is released

23. Glucagon and Its Functions
Effects on Glucose Metabolism
Glucagon increases gluconeogenesis
Glucagon activates adipose cell lipase-makes increased quantities of free fatty acids available
Inhibits the storage of triglycerides
In high concentrations-enhances the strength of the heart, increases blood flow in some tissues (kidney), enhances bile secretion, and inhibits gastric acid secretion

24. Glucagon and Its Functions
Regulation of Glucagon Secretion
Increased blood glucose inhibits glucagon
Increased blood amino acids stimulates glucagon
secretion
c. Exercise stimulates glucagon secretion

25. Glucagon and Its Functions
Regulation of Glucagon Secretion
Fig Approximate plasma glucagon concentration at different blood glucose levels

26. Glucagon and Its Functions
Somatostatin Inhibits Glucagon and Insulin Secretion
Almost all factors related to the ingestion of food stimulate somatostatin secretion (increased amino acids, fatty acids, GI hormones, blood glucose)
Acts locally within the islets to decrease secretion of insulin and glucagon
Decreases the motility of the stomach, duoenum, and gall bladder
Decreases secretion and absorption in the GI tract

27. Diabetes Mellitus
Diabetes Mellitus
Syndrome of impaired carbohydrate, protein, and fat metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to
insulin
Type I-insulin dependent diabetes mellitus; lack of insulin secretion
Type II-non insulin dependent diabetes mellitus; initially caused by the decreased sensitivity of tissues to insulin (insulin resistance)