Introduction to antidiabetic drugs: Insulin

Pharmacology lecture on insulin

1. antidiabetic drugs Insulin Pharmacology Roll 26-50 Moderator : Dr. Puja mam

2. Two chain polypeptide 51 amino acids MW about 6000. A-chain - 21 B-chain - 30 C-chain - 35

3. Glucosensor In β cells Glucose-6-Phosphate activates the glucosensor Glucosensor partially depolarizes the β cell Ca 2+ enflux causes release of insulin vesicles

4. Other insulin releasing stimulus amino acids fatty acids ketone bodies Incretins and glucagon (via cAMP) but glucose = principal regulator also stimulates synthesis of insulin.

5. Incretins: explained in pathology Eg. Glucagon-like peptide-1 (GLP1) glucose-dependent insulinotropic polypeptide (GIP) vasoactive intestinal peptide (VIP) pancreozymin-cholecystokinin, etc. Different incretin may mediate signal from different nutrient.

6. insulin release: Effect of hormones Somatostatin inhibits insulin + glucagon Glucagon stimulates of insulin + somatostatin Insulin inhibits glucagon Amylin (β cell polypeptide released with insulin) inhibits glucagon via brain

7. Neural control of insulin release Sympathetic α2 - decreases insulin release (decrease cAMP ) β2 - increases insulin (stimulating adenylyl cyclase) But α2 is predominant

8. Neural control of insulin release Parasympathetic Muscarinic - insulin secretion ( IP3/DAG  increased intracellular Ca2+  exocytosis)

9. Neural influences govern both basal + evoked insulin secretion Hence, blocking agents have opposite effects Primary central regulation = hypothalamus stimulation of ventrolateral nuclei - insulin release stimulation of ventromedial nuclei has the opposite effect.

10. Pulsatile release First Phase Glucose induces a brief pulse of insulin output (within 2 min) Second Phase Delayed but more sustained of insulin release.

11. Identify.....? BANTING AND BEST DISCOVERED INSULIN FROM DOG’S PANCREAS 1921

12. Insulin: Fun Facts? Pork insulin is more homologous to human insulin than is beef insulin. Basal condition ~1U insulin per hour Hyper insulinaemia per se has been implicated in causing angiopathy. exercise has insulin sparing effect

13. overall effect of insulin To dispose meal derived glucose, amino acids, fatty acids and favour storage of fuel.

14. Explained in pathology… Insulin signalling pathway Mechanism of action Effect of insulin on organs

15. Insulin’s Fate Insulin is distributed only extracellularly. Injected insulin or that from pancreas - metabolized primarily in liver and also in kidney and muscles. plasma t½ is 5–9 min.

16. iNTERACTIONS β adrenergic blockers Warning signs of hypoglycaemia ( β2 ) like palpitation, tremor and anxiety are masked. Thiazides, furosemide, corticosteroids, oral contraceptives, salbutamol, nifedipine raise blood sugar

17. Interactions Alcohol precipitate hypoglycaemia by depleting hepatic glycogen Lithium, high dose aspirin, theophylline hypoglycaemia by enhancing insulin secretion + glucose utilization.

18. Thanks Insulin Secretion Insulin

19. Quiz time

20. You injected glucagon in a gorilla. What hormones will be increased? Insulino only Insulin+somatostatin Somatostatin only None of the above 2

21. Incretins do not include Glucagon-like peptide-1 (GLP1) glucose-dependent insulinotropic polypeptide (GIP) vasoactive intestinal peptide (VIP) Insulin-like peptide pancreozymin-cholecystokinin 4

22. Glucosensor : Blocks Calcium channels Blocks potassium efflux Synthesises insulin All of the above 2

23. SUR1 is Sulphated glycolipid Synthesises insulin Regulates ATP sensitive K + channel All of the above 3

24. Beta agonists block hypoglycemia warning: True False F

25. Insulin distributes itself inside every cell and produces effect: True False F

26. Upcoming… Insulin analogues