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2 Pro-Insulin

3 Physiology and Biochemistry of Insulin GlucagonDr. 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 urineBoils and tendency to die in coma

6 1889: Minkowsky: Presence ofhypoglycemic 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 techniqueDown 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

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

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14 Excess Insulin Tumors of β cells Hypoglycemia during fastingFasting 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 proneAcute onset often with ketosis Sensitivity to exogenous insulin Destruction of pacreatic β cells

17 Symptoms of Type I DiabetesIncreased 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 DiabetesPeripheral 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

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

23 Methods of Inducing DiabetesAnti-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

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

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