This document discusses insulin and glucagon, including their discovery, structure, functions, mechanisms of action, and roles in diabetes. It provides information on: - The discovery of insulin in 1923 by Banting and Macleod who received the Nobel Prize, and the determination of insulin's primary structure by Sanger in 1954. - The types of diabetes (Type I, Type II, secondary), their causes, symptoms, prevalence, complications. - Insulin analogues created through genetic engineering like Lispro, Aspart, and Glargine that have altered onset and duration of action. - The discovery and roles of glucagon in glucose regulation, with basal levels, half-life, secretion

1. Anu. M. A
M.Sc. Sem II

3. Discovery
• Banting and Macleod
(the Nobel Prize
in Physiology or
Medicine) -1923
• Sanger –primary
structure- 1954.

6. Structure

7. Biosynthesis

8. Insulin release

9. Insulin oscillation

10. Insulin receptor

11. Plasma levels of insulin
• 10 µ units/ml
• After fasting – 5 µ units/mL
• Half life – 5 to 18 mins (approax.)
• MCR- 1000mL/min
• Insulin degradation- insulinases of kidney,
liver

12. Mechanism of action

15. DIABETES MELLITUS
• Primary
• Insulin-dependent (type I)
• Non-insulin dependent (type II)
• Secondary
• Ass. With pathological conditions-
pancreatitis, acromegaly, cushing’s syndrome

16. Type I (insulin-dependent)
• Auto immune disorder
• Antibodies destroy β cells
• Prevalence – 10 to 20 %
• Manifests before 40 years (usually between 12-
15 years)
• Juvenile onset diabetes
• Patients- usually lean
• Acute complication – ketoacidosis
• Symptoms- polyuria, polydypsia, polyphagia
• High mortality

17. Type II (insulin independent)
• Resistance of target tissues to insulin
• 80 to 90 % of diabetic population
• Onset after 40 years
• Adult onset diabetis
• Occur due to decrease in insulin receptor on
target cells
• Patients- usually obese
• Acute complication – hyperosmolar coma
• Low mortality

21. Insulin analogues
• Chemically and enzymatically modified
insulin
• Non-hexameric analogue
• Shifted isoelectric point- insulin

22. Lispro insulin
• First insulin analogue
• Fast acting
• Engineered through rDNA technology
• Lys, Pro residue on C terminal end of B chain
–reversed
• Trade name- Humalog

23. Insulin aspart
• Created by rDNA technology
• Proline (B 28) substituted with Asp
• Marketed by Novo Nordisk.
• Onset of action- 15 mins after injection
• Action peak – 45 to 90 mins

24. Insulin glargine
• +vely charged Arg added to C terminus of B
chain
• Isoelectric point shift from 5.4 to 6.7
• Marketed by Sanofi aventis.
• Trade name - Lantus

25. GLUCAGON

26. Discovery
• Kimball and Murlin
• Found glucagon in 1920
• described glucagon in 1923.
• amino acid sequence of glucagon- described
in the late-1950s.
• complete understanding of its role in
physiology and disease -established in the
1970s- by radio immuno assay.

27. Structure

28. Biosynthesis

29. Plasma levels
• Basal levels – fasting – 100- 150 pg/ml
• Half life – 6 mins
• Secretion rate – 100 to 150 µg/day
• Circulation – in unbound form

30. Actions
• Effect on carbohydrate metabolism
• On lipid metabolism
• On protein metabolism

31. Mechanism of action

32. Insulin – glucagon ratio
• Under basal conditions- molar ratio= 2.0
• Under fasting conditions = ˃ 0.5
• After a pure carbohydrate meal - ˂10

33. Regulation of secretion
• By Blood glucose level
• Plasma amino acids
• Free fatty acids and keto acids

34. Glucogonoma
• rare tumour of the alpha cells of the pancreas
• overproduction of glucagon
• enhances blood glucose levels through the
activation of anabolic (gluconeogenesis)
and catabolic processes (lipolysis).
• Treatment - administration of octreotide, a
somatostatin analog, which inhibits the
release of glucagon

35. HYPOGLYCEMIA vs HYPERGLYCEMIA