1. Dr. Hany Ahmed Assistant Professor of Physiology (MD, PhD) Al Maarefa Colleges (KSA) & Zagazig University (Egypt) Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit Dr. Hany Ahmed Assistant Professor of Physiology (MD, PhD) Al Maarefa Colleges (KSA) & Zagazig University (Egypt) Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit

2. The student should be able to:  Know pathways of fuel metabolism.  Know the cell types associated with the endocrine pancreas.  Discuss the regulation of glucagon synthesis and release from pancreatic alpha cells.  Know the actions of glucagon at the target tissue.  Describe the regulatory effects of insulin on the metabolism of carbohydrates, fats and proteins.  Describe the regulation of insulin secretion from pancreatic beta cells.  Know the actions of somatostatin at the target tissue.

3. PATHWAYS OF FUEL METABOLISM

4. METABOLIC FUEL IN THE BODY

5. Pancreas

6. THE ENDOCRINE PANCREAS The endocrine functions are limited to Islets of Langerhans (1- 2 millions). The islets contain 4 types of cells: 1)α cells (20-25%) secrete Glucagon (hyperglycemic). 2)β cells (60-70%) secrete Insulin (hypoglycemic). 3)δ cells (10%) secrete Somatostatin. 4)P c P cells (1%) secrete pancreatic polypeptide.

7. 1- GLUCAGON  It is a polypeptide hormone formed of 29 amino acids.  Glucagon is the hormone of “energy release“.  Actions: 1) ↑ Blood glucose level (= hyperglycemic) by: Increases glycogenolysis (immediate action & of short duration) & gluconeogenesis in liver (delayed response & long acting). It has No action on muscle glycogen or on peripheral utilization of glucose. 2) Stimulates lipolysis & ketogenesis: By activation of adipose cell lipase   blood fatty acids for energy production. The hormone inhibits triglycerides storage in liver.

10. GLUCAGON ACTIVITY

11. Control of glucagon secretion 1- Blood Glucose level:  Bl. glucose  stimulates alpha cells   glucagon secretion. 2- High concentration of amino acids: E.g. Alanine and Arginine after protein meal stimulates glucagon secretion (the same effect as insulin) i.e. amino acids are used in gluconeogenesis. 3- GIT hormones: CCK   glucagon secretion. Secretin   glucagon secretion. Protein meal (oral route) is more potent stimulus for glucagon secretion more than i.v. injection of amino acids. Why? 4- Somatostatin & insulin   glucagon secretion.

12. Action of insulin & glucagon during absorption of high protein meal

14. 2- INSULIN  It is a polypeptide hormone, composed of two chains of 51 amino acids connected by a disulfide linkages.  It is the hormone of “energy storage”

15. Insulin receptors  Insulin receptor is a glycoprotein with 300.000 MW found in cell membrane.  It is composed of 4 subunits: 2 alpha (lie outside cell membrane). 2 beta (penetrate cell membrane into cytoplasm).  Binding of insulin to 2 alpha subunits  autophosphorylation of 2 beta subunits  act as a local Tyrosine kinase  activate other enzymes. Thus insulin exerts its biological action.

16. Insulin receptors

17. Actions of Insulin

18. 1- On CHO metabolism Hypoglycemic hormone. Insulin increases the number of glucose transporters in the membrane; it may also increase the rate at each transporter. It stimulates Cell membrane permeability to glucose  rapid entry of glucose into cells. It stimulates Utilization of glucose in liver and muscles by helping phosphorylation to glucose-6-phosphate by glucokinase (in liver), also it stimulates glycolysis. It stimulates Glycogenesis & Inhibits Gluconeogenesis. Therefore, the net effect is  To increase glycogen synthesis in liver.  To decrease glucose in blood

19. On CHO metabolism In resting muscle: membrane is slightly permeable to glucose  muscle depends on fatty acids for its energy. During muscular exercise: muscle cell membrane becomes highly permeable to glucose  muscles utilize large amounts of glucose in absence of insulin )  GLUT 4 during exercise). After meals: there is excess insulin secretion due to hyperglycemia  rapid transport of glucose through muscle cell membrane and inhibition of fatty acid flow from adipose tissue. So, muscle depends on glucose utilization during this period.

21. 1.Tissues in which insulin facilitates glucose uptake (=insulin-sensitive cells):  Skeletal muscle, Cardiac muscle & Smooth muscle.  Adipose tissue, Leukocytes.  Crystalline lens of the eye.  Pituitary gland & Mammary gland.  Alpha cells of pancreatic islets. 2. Tissues in which insulin does not facilitate glucose uptake:  Brain (except probably part of hypothalamus).  Kidney tubules, Intestinal mucosa & Red blood cells.

22. 2- On Fat Metabolism Decrease blood fatty acid level & promotes Triglyceride storage. 1.Promotes entry of fatty acids into adipose tissue cell 2.Promotes entry of glucose into adipose tissue cell 3.Promotes synthesis of triglycerides from fatty acids and glycerol (Lipogenic) 4.Inhibits lipolysis as it inhibits hormone-sensitive lipase. 5.Inhibits release of fatty acids from adipose tissue.

23. 3- On Protein Metabolism  Promotes active transport of amino acids in muscles and other tissues. Insulin decreases blood amino acid level.  Stimulates protein synthesis in cell (anabolic).  Inhibits protein breakdown.

24. 4- Other actions 1.On growth: Helps in general growth along with other hormones. 2. On electrolytes: Causes increased Mg ++, K + & phosphate uptake by muscles thereby decreasing plasma K + levels.

25. Principal Actions of Insulin On Adipose tissue: 1)Increased glucose entry 2)Increased fatty acid synthesis 3)Increased glycerol phosphate synthesis 4)Increased triglyceride deposition 5)Activation of lipoprotein lipase 6)Inhibition of hormone-sensitive lipase 7) Increased K + uptake

26. Principal Actions of Insulin On Muscle 1)Increased glucose entry 2)Increased glycogen synthesis 3)Increased amino acid uptake 4)Increased protein synthesis in ribosomes 5)Decreased protein catabolism 6)Decreased release of gluconeogenic amino acids 7)Increased K+ uptake On Liver 1)Decreased ketogenesis 2)Increased protein synthesis 3)Increased lipid synthesis 4)Decreased glucose output due to decreased gluconeogenesis and increased gluocogen synthesis

28. Factors Controlling Insulin Secretion 1- Glucose level in blood:  Blood glucose 2 to 3 times than normal fasting level (70 - 100 mg %)   insulin secretion in two steps:  Rapid (first peak): Insulin output increases 10 times the resting value within 5 minutes. Followed by a sudden drop in 5 - 10 minutes. Due to immediate release of preformed stored insulin.  Delayed (plateau): Higher and continuing increase in insulin after 15 - 20 minutes. Reach a plateau for 2 - 3 hours. Due to new insulin formation by activation of enzyme system.

29. Factors Controlling Insulin Secretion 2- Amino acids: arginine & lysine are potent stimulators. 3- Hormones: Glucagon  stimulates beta cells   insulin secretion. Somatostatin  inhibits beta cells   insulin secretion. 4- GIT hormones: Glucagon Like Peptide - 1 (GLP-1), CCK and Gastric Inhibitory Peptide (GIP)   Insulin secretion. 5- Sympathetic stimulation: Stimulation of α - receptors   insulin secretion (Predominant). 6- Vagal stimulation & Ach   insulin secretion.

30. 30 Factors Controlling Insulin Secretion

31. 31 Blood Glucose and the Pancreatic Hormones Insulin Glucagon

32. Stimulation of insulin secretion by glucose via excitation- secretion coupling

33. 33 Importance of Maintaining Blood Glucose Within the Normal Range

34. 3- SOMATOSTATIN  Released from pancreatic D cells in direct response to increase in blood sugar and blood amino acids during absorption of a meal Inhibitory effect on both insulin and glucagon Decreases motility of stomach, duodenum and gallbladder Decreases secretion and absorption in gastrointestinal tract. Therefore, somatostatin: 1.Inhibits digetion and absorption of nutrients 2.Decreased utilization of absorbed nutrients by tissues 3.Extends the availability of nutrients for longer periods of time 34

35. 35 REGULATION OF INSULIN AND GLUCAGON BY SOMATOSTATIN  Somatostatin inhibits the release of both insulin and glucagon Its release, in turn, is stimulated by glucagon and inhibited by insulin

36. صنائع المعروف تقي مصارع السوء.. وصاحب المعروف لا يقع، فإذا وقع وجد متكأ. فقدِّم تَجِد..