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Insulin by Dr. Anurag Yadav
- 1. Presenter: Dr AnuragYadav Dept Of Biochemistry, FMMC
- 2. Insulin • Is apolypeptide hormone produce by β-cells of langerhans of pancreas. • It has profound influence on metabolism of Carbohydrates, fat & proteins. • It is considered as the anabolic hormone. Dept Of Biochemistry, FMMC
- 3. • It wasthe first hormone to be isolated, purified & synthesized. • First hormone to be sequenced • First hormone to be produced by recombinant DNA technology. Dept Of Biochemistry, FMMC
- 4. Structure • Human Insulincontain 51 aminoacids, arranged in TWO Polypeptide chains. • Chain A = 21 AA • Chain B = 30 AA • Two Interchain Disulfide bridge = A7-B7 & A20-B19. • Intrachain Disulfide link in chain A = 6-11. Dept Of Biochemistry, FMMC
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- 6. Synthesis • Gene forprotein synthesis is located on Chr 11 • Produced from β-cell of Langerhans of pancreas. • Synthesis involve two precursors – Preproinsulin = 108AA – Proinsulin = 86 AA Dept Of Biochemistry, FMMC
- 7. • These aresequentially degraded to form the active hormone Insulin and Connecting peptide (C-Peptide) • C-peptide has no biological activity, however its estimation in plasma serves as the useful index for endogenous production of insulin. • In β-cells, Insulin combines with Zinc to form a complex & stored in granules. Dept Of Biochemistry, FMMC
- 8. Regulation of Insulinsecretion • About 40-50Units secreted daily by Human pancreas. • Normal value is = 20-30μU/mL Dept Of Biochemistry, FMMC
- 9. Factors increasing thesecretion – Stimulating the secretion • Glucose • Aminoacids • GI Hormone (secretin, gastrin, pancreozymin) • Parasympatheic stimulation • Incretin hormone – Inhibiting secretion • Epinephrine • Alp-ha adrenergic stimulaion Dept Of Biochemistry, FMMC
- 10. Mechanism of actionof Insulin Insulin receptor mediated signal transduction Insulin receptor Signal transduction Insulin mediated glucose transport Insulin mediated enzyme synthesis Dept Of Biochemistry, FMMC
- 11. Mechanism of action •The insulin signaling pathway provide an excellent example for Recognition Hormone release Signal generation Effects Surface receptor and Tyrosine kinase mediated Dept Of Biochemistry, FMMC
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- 13. • Glucokinase • Pyruvatekinase • phosphofructokinase • Acetyl CoA carboxylase Insulin induces •Glyucose-6-P •Phosphoenolpyruvate carboxykinase •Fructose-6-P Insulin represses Dept Of Biochemistry, FMMC
- 14. Degradation of Insulin •Half life is 4-5mins. • A protease enzyme, namely insulinase degrades Insulin (mainly found in liver and kidney) Dept Of Biochemistry, FMMC
- 15. Metabolism effects ofinsulin Uptake of glucose by tissues Glycoly sis of glucose Hypogly cemic effect Lipogen esis Anti- lipotic effect Anti- ketogeni c effect Dept Of Biochemistry, FMMC
- 16. Metabolism effects ofinsulin • Glucose uptake by tissues. • Increase Glycolysis (utilization). • Decrease gluconeogenesis. Carbohydrate Metabolism • Favours synthesis of TAG. • Decrease lipolysis (hormone sensitive lipase) • Reduce ketogenesis (HMG CoA synthetase). • Increase utilization of acetyl CoA in Krebs Cycle. Lipid Metabolism • Enhance protein synthesis. • Anabolic hormone Protein metabolism Dept Of Biochemistry, FMMC
- 17. Disorders • Diabetes mellitus –Type I DM – Type II DM – Type 1.5 DM Dept Of Biochemistry, FMMC
- 18. Resistance • Insulin resistance(IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. • Measuring insulin resistance – Hyperinsulinemic euglycemic clamp (Gold std) – Modified insulin suppression test – HOMA (homeostatic model assessment), QUICKI (quantitative insulin sensitivity check index) Dept Of Biochemistry, FMMC
- 19. Utility of testin assessing the Deficiency status • Analysis for the Diagnosis & Monitoring of the Diabetes status – Blood Glucose (Fasting & PPBS) – OGTC (Oral Glucose tolerance test) – Glycated Hb (HbA1c) – Urine Glucose – Sr- Insulin, C-Peptide. Dept Of Biochemistry, FMMC
- 20. Approaches to preventingDiabetes Physical activity Life style changes Mental stress handling Hypoglycemic Drugs/insulin Dept Of Biochemistry, FMMC
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- 24. • Reference – Vasudevan-Textbookof Biochemistry – Harper’s-Illustrated Biochemistry – Gyton-Human Physiology – Internet sources Dept Of Biochemistry, FMMC