Download to read offline
More Related Content
![INSULIN AND OTHER ANTIDIABETEC DRUGS [Autosaved] [Autosaved].pptx](https://cdn.slidesharecdn.com/ss_thumbnails/insulinandotherantidiabetecdrugsautosavedautosaved-220731124033-32b4f1bb-thumbnail.jpg?width=640&height=640&fit=bounds)
Similar to Insulin metabolism structure synthesis metabolic error
Insulin metabolism structure synthesis metabolic error
- 1. Structure of insulin proteinhormone with 2 polypeptide chains. The A chain has 21 amino acids and B chain has 30 amino acids. These two chains are joined together by two interchain disulphide bonds, between A7 to B7 and A20 to B19
- 2. . Thereis also an intrachain disulphide link in A chain between 6th and11th amino acids
- 3. H2N-G --------- C— C — T — S —I — C-------- C — Asn — COOH 1 6 7 8 9 10 11 20 21 | | S S S S | A chain or Gly chain H2N--Phe--------------C----------------------------- 1 7 C-----Lys--Thr--COOH 19 29 30 B chain or Phe chain Ala- Ser- Val (Bovine) Thr- Ser- Ile (Pig) (Bovine)—Ala 30 (Pig) — Ala 30 ----------S---S----- INSULIN primary structure Interchain di-sulphide linkage Intrachain
- 4. Biosynthesis of insulin i. Insulin is a protein synthesized and secreted by the betacells of the islets of Langerhans of the pancreas.
- 5. ii. Theinsulin is synthesized as a larger precursor polypeptide chain, the pre-pro- insulin. It has 109 amino acids. It is rapidly converted to pro-insulin in the endoplasmic reticulum by removal of leader sequenceof 23 amino acid residues.
- 6. Glu- 31 Lys Arg Gly -1 Glu-1 Arg Arg Thr-30 7 20 21 C C Asn Phe C C 1 7 19 A chain 21 B chain 30 C chain (connecting) 31 PRO--INSULIN
- 7. iii. Theproinsulin with 86 amino acids is transported toGolgi apparatus where it is cleaved by a protease Thus C-peptide or connecting peptide with33 amino acids is removed.
- 8. Secretion of insulin The insulin is packed into granules. The molecules take shape of a hexamer with 2 zinc ions and one calcium ion.
- 9. Approximately 50units of insulin is secreted per day. Normal insulin level in blood is 5-15 microunits/ml. Proinsulin contributes 5 to 10% of the total insulin measured in plasma. Proinsulin has about one-third biological activity as that of insulin
- 10. Insulin andC-peptide are synthesized and secreted in equimolar quantities. Therefore, measurement of C-peptide is an index of rate of secretion of insulin. Mutations causing changes in amino acid sequence at the cleavage points can lead to familial pro-insulinemia.
- 11. Mechanism of insulinsecretion
- 12. Glucose entry GluT2 beta cell Mechanism ofinsulin secretion
- 13. Glucose entry GluT2 beta cell Mechanism ofinsulin secretion Glucose more; ATP more K-ATP Channel
- 14. Glucose entry GluT2 K-ATP Channel Calciumentry beta cell Mechanism of insulin secretion Glucose more; ATP more
- 15. Glucose entry GluT2 K-ATP Channel Calciumentry beta cell Mechanism of insulin secretion Glucose more; ATP more Insulin in granules secreted outside
- 16. Glucose is themajor stimulant of insulin secretion GluT 2 receptors Cyclic AMP and calcium causes the insulin secretion Other stimulants proteins, amino acids leucine and arginine Tolbutamide will stimulate insulin secretion
- 17. Insulin half lifeis only 5 minutes About 40 – 50 units of insulin secreted per day Measurement of Insulin and C – peptide by RIA or ELISA methods
- 18.
- 19. Alpha and beta unitsare combined by disulphide linkages Membrane Beta subunits Alpha subunit
- 20. Insulin binding site Alphaand beta units are combined by disulphide linkages Membrane Beta subunits Alpha subunit
- 21. Insulin binding site Alphaand beta units are combined by disulphide linkages Membrane Beta subunits Tyrosine kinase domain; catalytic activity switched on when insulin binds to receptor. Then tyrosine residues are phosphorylated Alpha subunit
- 22. Physiological Actions ofInsulin Regulation of the metabolism of carbohydrates, lipids and proteins. 1. Glucose Uptake Insulin facilitates Facilitated diffusion of glucose in muscle. Transporter, GIuT4 is insulin dependent Glucose uptake in liver (by GluT2) is independent of insulin.
- 23. 2. Utilisation ofGlucose 3. Insulin favours storage of glucose Glycolysis increased key glycolytic enzymes (glucokinase, phosphofructokinase and pyruvate kinase) Glycogen synthesis increased Glycogen synthase
- 24. 4. Lipogenesis increased AcetylCoA Carboxylase Glucose-6-Phosphate dehydrogenase (NADPH) 5. Anti-lipolytic effect Hormone sensitive lipase
- 25. 6.Gluconeogenesis Decreased Key gluconeogenicenzymes Pyruvate kinase Phospho enol pyruvate carboxy kinase Fructose 1,6 bis phosphatase Glucose 6 phosphatase 8. Anabolic Effect 7. Anti-ketogenic Effect HMG CoA synthase
- 26. Metabolism Insulin Glucagon Glycolysisstimulate inhibit Glycogenolysis inactivate activate
- 27. Metabolism Insulin Glucagon Glycolysisstimulate inhibit Glycogenolysis inactivate activate Gluconeogenesis inhibit stimulate Glycogen synthesis activate inhibit
- 28. Metabolism Insulin Glucagon Glycolysisstimulate inhibit Glycogenolysis inactivate activate Gluconeogenesis inhibit stimulate Glycogen synthesis activate inhibit Lipolysis inhibit stimulate Ketogenesis inhibit stimulate
- 29. Metabolism Insulin Glucagon Glycolysisstimulate inhibit Glycogenolysis inactivate activate Gluconeogenesis inhibit stimulate Glycogen synthesis activate inhibit Lipolysis inhibit stimulate Ketogenesis inhibit stimulate Protein anabolism catabolism
- 30. Metabolism Insulin Glucagon Glycolysisstimulate inhibit Glycogenolysis inactivate activate Gluconeogenesis inhibit stimulate Glycogen synthesis activate inhibit Lipolysis inhibit stimulate Ketogenesis inhibit stimulate Protein anabolism catabolism Blood sugar level decrease increase
- 31. Hyperglycemia Insulin Lowers blood sugar Glucose uptakeby tissue cells Glycogen synthesis Liver Pancreas
- 32.
- 33. Raises blood sugarHyperglycemia Glucagon Insulin Hypoglycemia Lowers blood sugar Glucose uptake by tissue cells Glycogen synthesis Liver Glycogenolysis Pancreas