Islets of Langerhan. Prof. K. Sivapalan. 08-01-14Islets of Langerhan2 Structure. Blooed supply-...

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Islets of Langerhan. Prof. K. Sivapalan

Transcript of Islets of Langerhan. Prof. K. Sivapalan. 08-01-14Islets of Langerhan2 Structure. Blooed supply-...

Page 1: Islets of Langerhan. Prof. K. Sivapalan. 08-01-14Islets of Langerhan2 Structure. Blooed supply- Drainage through portal vein to liver and through hepatic.

Islets of Langerhan.

Prof. K. Sivapalan

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Structure.

• Blooed supply-• Drainage through

portal vein to liver and through hepatic vein into IVC.

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Histology.

• A cells 20 % [glucogon]

• B cells 50% [Insulin]• D cells 8%

[somatostatin]• F cells [pancreatic

polypeptide]

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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.

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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.

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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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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.

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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.

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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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Insulin and Growth

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Regulation of insulin secretion.

• Feed back by glucose.

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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.

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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

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Effects of removing pancreas.

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Effects of insulin deficiency.

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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.

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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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Changes in hyperglycaemic coma

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Retinal Changes in Diabetes.

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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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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.

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Regulation of Glucagon Secretion

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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.

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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.