Islets of Langerhan. Prof. K. Sivapalan

Islets of Langerhan2 Structure. Blooed supply- Drainage through portal vein to liver and through hepatic vein into IVC.

Islets of Langerhan3 Histology. A cells 20 % [glucogon] B cells 50% [Insulin] D cells 8% [somatostatin] F cells [pancreatic polypeptide]

Islets of Langerhan4 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 Langerhan5 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 Langerhan6 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

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Islets of Langerhan8 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 Langerhan9 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 Langerhan10 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.

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Islets of Langerhan12 Insulin and Growth

Islets of Langerhan13 Regulation of insulin secretion. Feed back by glucose.

Islets of Langerhan14 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 Langerhan15 Factors affecting insulin secretion. 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

Islets of Langerhan16 Effects of removing pancreas.

Islets of Langerhan17 Effects of insulin deficiency.

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, acanthosis nigricans Islets of Langerhan18

Islets of Langerhan19 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.

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Islets of Langerhan21 Changes in hyperglycaemic coma

Islets of Langerhan22 Retinal Changes in Diabetes.

Islets of Langerhan23 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.

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Islets of Langerhan25 Glucagone. Peptide with 29 aminoacids, half life minutes. From A cells of pancreas and gastric and duodenal mucosa. Actions- just opposite of insulin.

Islets of Langerhan26 Regulation of Glucagon Secretion

Islets of Langerhan27 Factors Affecting Glucagone secretion. 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.

Islets of Langerhan28 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.