Islets of Langerhan.

1. Islets of Langerhan. Prof. K. Sivapalan

2. Structure. • Blooed supply- • Drainage through portal vein to liver and through hepatic vein into IVC. Islets of Langerhan

3. Histology. • A cells 20 % [glucogon] • B cells 50% [Insulin] • D cells 8% [somatostatin] • F cells [pancreatic polypeptide] Islets of Langerhan

4. Insulin secretion. • Synthesized as one long poly peptide. • Folded by disulfide bonds. • A portion is removed in middle. • Result is a molecule with A and B peptide chains. • Half life- 5 minutes. Islets of Langerhan

5. Structure of Insulin • A chain – 22, B chain – 30 amino acids. • Animal insulins vary in less than 4 amino acids. • Insulin from animals can be antigenic. • Pork insulin is less antigenic compared to beef insulin. • Human insulin is manufactured by recombinant DNA technology in bacteria. Islets of Langerhan

6. Mechanism of Actions of Insulin • Insulin receptors are found in almost all cells. • Insulin binds to the receptor. • The receptor activates several different actions depending on the nature of the cell. • There is similar action by Insulin Like Growth Factors- ? significance Islets of Langerhan

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8. Actions of Insulin on Carbohydrate Metabolism.. • Glucose transporters are increased by increased levels of insulin. • Glucose enters cells by facilitated diffusion- exceptions are, brain, Small intestinal epithelium, PCT in kidney. • ? Glucose entry in Liver and red cell • Glycogen storage increased in Liver and Muscle. Increases glycogen synthesis and reduces glycolytic enzymes. Islets of Langerhan

9. Actions of Insulin on Fat and Protein Metabolism • Increases lipogenesis in liver and adipose tissue. • Reduces lypolysis. • Activates transport of Amino Acids into cells. • Increases protein synthesis by accelerated translation. • * increases intracellular potassium. Islets of Langerhan

10. Insulin Action [Timed]: • Rapid- [Seconds] • Increased transport of glucose, amino acids, and K+ into insulin sensitive cells. • Intermediate- [minutes] • Stimulation of protein synthesis. • Inhibition of protein degradation. • Activation of glycogen synthetase. • Inhibition of Phosphorylase and gluconeogenic enzymes. • Delayed [hours] • Increase in mRNA for lipogenic and other enzymes. Islets of Langerhan

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12. Insulin and Growth Islets of Langerhan

13. Regulation of insulin secretion. • Feed back by glucose. Islets of Langerhan

14. Sudden increase of glucose. • Sudden increase of blood glucose results in immediate rise in blood insulin and a second slow increase. • ? Risk of fast food and benefit of natural food by slow digestion and steady absorption. Islets of Langerhan

15. Stimulators. glucose. Mannose. Aminoacids. Intestinal hormons Ketoacids. Acetyle choline Glucagon β adrenergic stimulators. Theophyline Sulfonylureas. Inhibitors Somatostatin. 2-deoxyglucose. α adrenergic stimulators. β blockers. Diazoxide Thiazide diuretics K+ depletion Factors affecting insulin secretion. Islets of Langerhan

16. Effects of removing pancreas. Islets of Langerhan

17. Effects of insulin deficiency. Islets of Langerhan

18. Causes of Diabetes • Primary- primarily pancreatic problem • Secondary- other diseases resulting in DM • Type I- autoimmune, young age (insulin deficiency) • Type II- main determinants- age, obesity, ethnicity and family history. (insulin resistance) • Metabolic syndrome- hypertension, obesity, hypertriglyceridaemia, decreased HDL, acanthosisnigricans. Islets of Langerhan

19. Diabetes Mellitus. • Hyperglycemia, intracellular glucose deficiency • Polyurea, (glycoseurea), Polydipsia. • Weight loss, Polyphagia • Retinopathy, neuropathy, erectile dysfunction • Arterial disease- MI, Gangrene • Poor resistance to infection- Skin infections • Ketosis, acidosis, coma. • Impaired glucose tolerance. Islets of Langerhan

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21. Changes in hyperglycaemic coma Islets of Langerhan

22. Retinal Changes in Diabetes. Islets of Langerhan

23. Hyperinsulinism. • Cause- insulinoma or injection (accidental overdose or under eating). • Early indications- tremor, palpitation, anxiety. • Confusion, weakness, dizziness, hunger, convulsions, coma, death within a few minutes. • Glucose need for brain- 1 mg/min/kg body weight (100g/day for 70 kg man) • It is a Medical emergency. • * Importance of carrying glucose and diagnosis card if on insulin injection. Islets of Langerhan

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25. Glucagone. • Peptide with 29 aminoacids, half life- 5-10 minutes. • From A cells of pancreas and gastric and duodenal mucosa. • Actions- just opposite of insulin. Islets of Langerhan

26. Regulation of Glucagon Secretion Islets of Langerhan

27. Stimulators. Amino acids. [glucogenic] CCK, Gastrin.* Cortisol Exercise. Infections. Stress. β adrenergic stimulators. Theophyline* Acetyl choline.* Inhibitors. Glucose [insulin] Somatostatin. Secretin FFA Ketons Insulin Phenytoin α adrenergic stimulators GABA. Factors Affecting Glucagone secretion. Islets of Langerhan

28. Other islet cell hormones. Somatostatin. • Inhibits secretion of insulin and glucagon. • Excess secretion can cause hyperglycemia. Pancreatic polypeptide. • Secretion increased by parasympathetic, protein meal, fasting, exercise, hypoglycemia. • Secretion decreased by somatostatin and IV glucose. • Action- ?slow absorption. Islets of Langerhan