biochemistry of Insulin and diabetes

biochemical and physiological aspects of insulin

1. Insulin Hamza Saeed Bhinder 152

2. Layout What i s Insulin Chemistry Biosynthesis Catabolism Mechanism of action Metabolic roles Regulation of Insulin IGF & Insulin Analogues Clinical Correlates References & Acknowledgements

3. A protein hormone secreted by the Beta cells of Islets of Langerhans of Pancreas that play a major role in the metabolism of Carbohydrate, fats and proteins Major Anabolic Hormone

4. C hemistry Of Insulin Protein hormone (12000-48000 MW) 2 polypeptide chains A-chain (21 A.A) & B-Chain (30 A.A) 2 disulphide bridges

5. Bio-Synthesis Synthesis of PreproInsulin (11500 Mw &109 AA) in RER Conversion of preproinsulin into proinsulin (9000 Mw & 86 AA) in ER Conversion of ProInsulin to Insulin and C peptide in Golgi appratus Note C peptide has no Insulin activity. Measurement of C peptide is a diagnostic tool in type 1 D iabetes Mellitus.

6. Catabolism of Insulin Half Life : 6 min Insulinase catabolize Insulin in liver and kidney by cleaving S-S bond

7. Oral Insulin ?

8. Mechanism Of Action Binding of Insulin with Alpha receptors Auto-phosphorylation of Beta receptors Activation of Tyrosine Kinase Phosphorylation of Insulin receptor substrates (IRS) Translocation of multiple intracellular vesicle to cell membrane where glucose transporters facilitate glucose uptake More permeability to AA, K+ and Phosphate ions Slow effects on Translation and Transcription

9. Metabolic Role Of Insulin Action on Carbohydrate Metabolism Glucose uptake Glycolyis Glycogenesis Glycogenolysis Gluconeogenesis

10. Action on Lipid Metabolism Synthesis of TGs Synthesis of Fatty Acids Lipolysis Ketogenisis

11. Action on Protein Metabolism Amino Acid Uptake Transcription Translation Synthesis of protein Catabolism of protein Gluconeogenesis

12. Action on Mineral Metabolism Conc. Of K+ & Inorganic P ion in Blood decreases due to enhanced glycogenesis and phosphorylation of glucose Action on growth and cell replication Along with growth hormone acts synergistically to promote growth. Increase DNA replication

13. Brief Summary

14. Regulation of Insulin Stimulating Factor Blood glucose Free fatty acids Amino Acids GIT hormones Glucagon Growth Hormones Cortisol Beta adrenergic stimulation Insulin resistance (Obesity) Sulphonyl Drugs

15. Inhibiting Factors Decreased Blood Glucose Fasting Somatostatin Alpha Adrenergic activity Leptin

16. IGF Insulin analogues These are Insulin like growth factors produced by the liver in response to GH Interact with insulin to cause cell growth and replication Synthesis by Recombinant DNA technology 3 types Short acting Intermidiate acting Long acting

17. Clinical Correlates Insulinoma Increase insulin secretion resulting in hypoglycemia caused by adenomas of islets of langerhans is called Insulinoma (hyper Insulinism ) Ex c ess insulin hypoglycemia Depressed CNS metabolism Insulin Shock Stages of Insulin Shock 1- Blood glucose 50-70mg/100ml, CNS excitability 2- Blood Glucose 50-20mg/ml, convulsions and loss of consciousness

18. Difference Between Diabetic and Hypoglycemic Coma 3- Blood glucose <20 mg/100ml , Hypoglycemic coma Hypo Glycemic Coma Diabetic Coma Due to decrease blood glucose <20mg/100ml No smell in breath No kussmaul Breathing Treated By Glucose Due to Acidosis Acetone smell in breath Kussmaul Breathing Treated by Insulin

19. Diabetes Mellitus A syndrome of impaired CHO, Fat and protein metabolism caused by either lack of Insulin secretion or decreased sensitivity of Insulin to tissues 2 types Type 1 IDDM Type 2 NIDDM

20. Garry Hall Jr. Olympic Swimming Medalist A Patient of Diabetes Mellitus Type 1

21. Type 1 Diabetes (IDDM) Juvenile Diabetes Definition This is a disease characterize by almost total deficiency of Insulin due to destruction of B-cells. Causes Environmental i.e. viral infection. Genetic i.e. auto-immune destruction of B-cells.

22. Sign And Symptoms Polyuria Polydipsia Polyphagia Diabetic Ketoacidosis Acetone Breath Vision Changes Unexplainable Fatigue Poor wound healing Foot ulcers Further Diabetic complications including Neuropathy, MI.

23. Metabolic changes: 1.Hyperglycemia 2.Ketosis 3.Hypertriacylglycerolemia.

24. Nicole Jhonson Miss America 1999 Patient of Diabetes type 1

25. Diagnosis: 1.Glycosuria,renal threshold is 180mg/100ml. 2.Fasting blood glucose level >126mg/100ml, commonly acccompanied by ketoacidosis. 3.Level of HbA1c often used to check effectiveness of treatment. (normal 3-5%)

26. Treatment: 1.Insulin Injections 2.Insulin Pumps release bolus doses of insulin (several units at a time) at meals and at times when blood glucose is too high, based on programming done by the user.

27. Insulin Pump Jason Johnson Detroit Tigers Pitcher Type 1 diabetes diagnosed at age 11 Wears insulin pump on field

28. References Textbook of Medical biochemistry by MN Chatterjae 8 th edition page no 581-586 Lenhingers principles of Biochemisitry 6 th edition page no 934-964 Lippincotts Illustrated review of biochemistry 6 th edition page 338-341 Textbook of Medical Physiology by Guyton and Hall page no 939-954 Wikipedia.com

29. Acknowledgments Allah Almighty Holy Prophet PBUH My Parents My Teachers My Friends; Hamza,Rashid , Usama , Itban , Asad , Junaid and Annus .