Pro-Insulin

2. Pro-Insulin

3. Physiology and Biochemistry of Insulin Glucagon Dr. Mohammed Kalimi And

4. Release of Insulin • ↑ Blood glucose • ↑ Glucose transport into β cells of pancreas • ↑ Glucose transporter proteins • ↑ Glucose oxidation • ↑ ATP production • Closure of potassium channels • ↑ Intracellular calcium • ↑ Release of insulin by exocytosis

5. Diabetes Mellitus • ↑ Plasma glucose • Large amount of sweet urine • Boils and tendency to die in coma

6. 1889: Minkowsky: Presence of hypoglycemic factor in pancreas • 1922: Benting and Best- Discovery of • insulin • 1959: Sanger: Chemical analysis of insulin (51 amino acids peptide)  1967: Steiner: Proinsulin • 1977: Rosalyn Yalow: Development of Radio Immuno Assay (RIA)

7. Human insulin production by recombinant DNA technique • Down regulation of insulin receptor • Insulin receptor has intrinsic tyrosine phospho kinase activity • Insulin pumps (including nasal spray) • Stem cell research

8. Insulin release • ↑ Blood glucose (hyperglycemia) • ↑ Plasma amino acids (lysine, arginine) • Diet • Vagus stimulation: acetylcholine • Sulfonylureas (hypoglycemic agent) • GIP and GLP-1 (glucagon-like peptide I)

9. Insulin Inhibition • Somatostatin • Catecholamines • Fasting • Exercise • Leptin

10. ↑Insulin •  Glucose •  Amino acids •  FFA •  Ketoacids ↑ Glucose transport, FFA transport, Amino acids transport ↑ Cell growth (RNA, DNA and protein synthesis), Differentiation

12. Insulin Mechanism Insulin – Receptor Complex  p- IRS   PI-3 kinase G-Ras  MAPK  Gene Expression

14. Excess Insulin • Tumors of β cells • Hypoglycemia during fasting • Fasting releases catecholamines • Rapid heart rate, sweating, hunger and nervousness • Coma, brain damage

15. Primary Diabetes • Type I (Juvenile) • Type II (Adult onset) • Diabetes during pregnancy

16. Diabetes Type I • 10% of all people • Thin, young, ketosis prone • Acute onset often with ketosis • Sensitivity to exogenous insulin • Destruction of pacreatic β cells

17. Symptoms of Type I Diabetes • Increased Hunger • Increased Thirst • Frequent Urination • Fatique • Weight Loss (negative nitrogen balance)

18. Type II Diabetes • Adult , often linked with obesity, hypertension, dyslipidemia, aging sedentary life style or genomic predisposition • Defects in insulin secretion and action (defective insulin receptor or post receptor defect) • Increased glucose output from the liver

19. Symptoms and complications of Type II Diabetes • Peripheral insulin resistance • Increased hunger (polyphagia), Increased thirst (polydispia), frequent urination • Frequent infections, cataract and blindness, numbness or tingling in hands and feet ( amputations), neuropathy, retinopathy and vascular diseases • Problems with pregnancy • Impotence

20. Secondary Diabetes Thyrotoxicosis Acromegaly Cushing’s syndrome Destruction of pancreas

22. Contributions of diabetogenic hormones • Effects of hypophysectomy •  Plasma ACTH and glucocorticoid secretion,symptoms of diabetes • Effects of pituitary extracts and glucocorticoids,↑ symptoms of diabetes

23. Methods of Inducing Diabetes • Anti-insulin serum • Alloxan and Streptozotocin • Pancreatectomy • Viral infection (coxsackie, mumps)

24. Glucagon • ↑ Glycogenolysis • ↑ Gluconeogenesis • ↑ Lipolysis

25. Blood Glucagon Insulin ↑ Glucose  Glucose ↑ FFA  FFA ↑ Ketoacids  Ketoacids  Aminoacids  Aminoacids

26. Glucagon Release • Hypoglycemia • ↑ Plasma amino acids • Stress and exercise

27. Glucagon Inhibition • Somatostatin • Insulin • ↑ Blood glucose (hyperglycemia) • ↑ Blood FFA

28. Tumors of α Cells • Excess Glucagon Levels • Weight loss • ↑ Plasma glucose, FFA, and ketoacids and  Plasma amino acids

30. Somatostatin Release • ↑ Plasma glucose, amino acids, FFA and GI hormones