Islets of Langerhan. Prof. K. Sivapalan. 08-01-14Islets of Langerhan2 Structure. Blooed supply-...
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Transcript of Islets of Langerhan. Prof. K. Sivapalan. 08-01-14Islets of Langerhan2 Structure. Blooed supply-...
Islets of Langerhan.
Prof. K. Sivapalan
08-01-14 Islets of Langerhan 2
Structure.
• Blooed supply-• Drainage through
portal vein to liver and through hepatic vein into IVC.
08-01-14 Islets of Langerhan 3
Histology.
• A cells 20 % [glucogon]
• B cells 50% [Insulin]• D cells 8%
[somatostatin]• F cells [pancreatic
polypeptide]
08-01-14 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.
08-01-14 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.
08-01-14 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
08-01-14 Islets of Langerhan 7
08-01-14 Islets of Langerhan 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.
08-01-14 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.
08-01-14 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.
08-01-14 Islets of Langerhan 11
08-01-14 Islets of Langerhan 12
Insulin and Growth
08-01-14 Islets of Langerhan 13
Regulation of insulin secretion.
• Feed back by glucose.
08-01-14 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.
08-01-14 Islets of Langerhan 15
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
08-01-14 Islets of Langerhan 16
Effects of removing pancreas.
08-01-14 Islets of Langerhan 17
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.
08-01-14 Islets of Langerhan 18
08-01-14 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.
08-01-14 Islets of Langerhan 20
08-01-14 Islets of Langerhan 21
Changes in hyperglycaemic coma
08-01-14 Islets of Langerhan 22
Retinal Changes in Diabetes.
08-01-14 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.
08-01-14 Islets of Langerhan 24
08-01-14 Islets of Langerhan 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.
08-01-14 Islets of Langerhan 26
Regulation of Glucagon Secretion
08-01-14 Islets of Langerhan 27
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.
08-01-14 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.