INSULIN AND GLUCAGON.pptx

INSULIN AND GLUCAGON

1. INSULIN AND GLUCAGON Anu . M. A M.Sc. Sem II

2. INSULIN

3. D iscovery Banting and Macleod (the Nobel Prize in Physiology or Medicine) -1923 Sanger –primary structure- 1954.

4. Structure

5. Biosynthesis

6. Insulin release

7. Insulin oscillation

8. Insulin receptor

9. Plasma levels of insulin 10 µ units/ml After fasting – 5 µ units/ mL Half life – 5 to 18 mins ( approax .) MCR- 1000mL/min Insulin degradation- insulinases of kidney, liver

10. Mechanism of action

11. DIABETES MELLITUS Primary Insulin-dependent (type I) Non-insulin dependent (type II) Secondary Ass. With pathological conditions- pancreatitis, acromegaly , cushing’s syndrome

12. Type I (insulin-dependent) Auto immune disorder Antibodies destroy β cells Prevalence – 10 to 20 % Manifests before 40 years (usually between 12- 15 years) Juvenile onset diabetes Patients- usually lean Acute complication – ketoacidosis Symptoms- polyuria , polydypsia , polyphagia High mortality

13. Type II (insulin independent) Resistance of target tissues to insulin 80 to 90 % of diabetic population Onset after 40 years Adult onset diabetis Occur due to decrease in insulin receptor on target cells Patients- usually obese Acute complication – hyperosmolar coma Low mortality

14. Insulin analogues Chemically and enzymatically modified insulin Non- hexameric analogue Shifted isoelectric point- insulin

15. Lispro insulin First insulin analogue Fast acting Engineered through rDNA technology Lys, Pro residue on C terminal end of B chain –reversed Trade name- Humalog

16. Insulin aspart Created by rDNA technology Proline (B 28) substituted with Asp Marketed by Novo Nordisk. Onset of action- 15 mins after injection Action peak – 45 to 90 mins

17. Insulin glargine + vely charged Arg added to C terminus of B chain Isoelectric point shift from 5.4 to 6.7 Marketed by Sanofi aventis . Trade name - Lantus

18. GLUCAGON

19. D iscovery Kimball and Murlin Found glucagon in 1920 described glucagon in 1923. amino acid sequence of glucagon- described in the late-1950s. complete understanding of its role in physiology and disease -established in the 1970s- by radio immuno assay.

20. Structure

21. Biosynthesis

22. Plasma levels Basal levels – fasting – 100- 150 pg/ml Half life – 6 mins Secretion rate – 100 to 150 µg/day Circulation – in unbound form

23. A ctions Effect on carbohydrate metabolism On lipid metabolism On protein metabolism

24. Mechanism of action

25. Insulin – glucagon ratio Under basal conditions- molar ratio= 2.0 Under fasting conditions = ˃ 0.5 After a pure carbohydrate meal - ˂10

26. Regulation of secretion By Blood glucose level P lasma amino acids Free fatty acids and keto acids

27. Glucogonoma rare  tumour  of the alpha cells of the  pancreas overproduction of   glucagon enhances  blood glucose  levels through the activation of anabolic ( gluconeogenesis ) and catabolic processes ( lipolysis ).   Treatment - administration of  octreotide , a somatostatin analog, which inhibits the release of glucagon

28. HYPOGLYCEMIA vs HYPERGLYCEMIA

29. THANK YOU