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Insulin Physiology: From Release to Effects on Glucose Metabolism and Diabetes Types

Explore the intricate process of insulin release, its effects on glucose metabolism, and the dynamics of different types of diabetes. Understand pro-insulin mechanisms, glucagon regulation, and the pathophysiology of diabetes mellitus. Learn about primary and secondary diabetes, symptoms, complications, and potential inducers of diabetes. Delve into the role of glucagon, blood glucose regulation, and the interplay between insulin and glucagon in maintaining metabolic balance. Gain insights into the complexities of diabetes management, mechanisms of insulin action, and the impact of hormonal interactions on glucose homeostasis.

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Insulin Physiology: From Release to Effects on Glucose Metabolism and Diabetes Types

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  1. Pro-Insulin

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

  3. 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

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

  5. 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)

  6. 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

  7. 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)

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

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

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

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

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

  13. 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

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

  15. 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

  16. 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

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

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

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

  20. Glucagon • ↑ Glycogenolysis • ↑ Gluconeogenesis • ↑ Lipolysis

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

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

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

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

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

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