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