4.  Introduction
 History
 Structure of insulin
 Biosynthesis
 Transport and catabolism
 Degradation
 Release of insulin
 Effects of insulin
 Clinical coorelations

5. INTRODUCTION
Insulin
> protein hormone
> by islets of langerhans
> pancreas
Anabolic hormone
> growth & development

6. HISTORY
• Canadian scientist
(1921)
–Fredrick G. Banting
–Charles H. Best
• extracted insulin
–from dog’s pancreas

7. STRUCTURE OF INSULIN
• Insulin
– Polypeptide hormone
– 51 amino acids
– Two chains
• A chain 21 a.a.
• B chain 30 a.a.
• Held by interchange disulfide
bridges

9. BIOSYNTHESIS OF
INSULIN
 Synthesis of Preproinsulin.
 Conversion of preproinsulin to
proinsulin.
 Conversion of proinsulin to insulin.

10. GENETICS OF INSULIN SYNTHESIS
 The proinsulin precursor of
insulin is encoded by the INS
gene

11. Preproinsulin
M.W 11500
109 A.A

12. Proinsulin
M.W 9000
86 A.A

13. Insulin (21+30 A.A)

14. Human proinsulin and its conversion to insulin.

15. CATABOLISM OF
INSULIN
 Half life: 3-5 minutes
 Major organs of degradation
> Liver.
>Kidney.
>Placenta.
 50% of insulin removed in a single pass through
liver.
MECHANISM :
 Insulin specific protease.
 Glutathione insulin transhydrogenase (Insulinase

19. Regulation of Insulin
Secretion

20. Correlation Between Plasma
Glucose & Insulin Levels

22. BIOLOGICAL EFFECTS OF
INSULIN

24. Effect on carbohydrate
metabolism
⇑ Glucose uptake
– Skeletal muscles
– Cardiac muscles
– Adipose tissue
– Mammary glands

25. Effect on carbohydrate
metabolism (contd)
 In s u lin in d e p e n d e n t t is s u e s
 B r a in
 RB C
 Te s t i s
 K id n e y
 R e t in a
 In t e s t in a l m u c o s a l c e lls

26. INSULIN MEDIATED
GLUCOSE UP TAKE

27. CARBOHYDRATE METABOLISM
Metabolism Net Effect Effect on important enzyme
Glycolysis Increased Glucokinase
Phosphofructokinase
Pyruvate kinase
Glycogenesis Increased Glycogen synthatase
HMP shunt Increased Glucose 6-phosphate
dehydrogenase
Gluconeogenisis Decreased Pyruvate carboxylase
Phosphoenol Pyruvate
carboxylakinase
Glucose 6-phosphatase
Glycogenolysis Decreased Glycogen phosphorylase

28. Lipid Metabolism
Metabolism Net effect Effect on important
enzymes
Lipogenesis Increased
DeNovo FA Synthesis Increased Acetyl CoA carboxylase
Avalbility of NADPH
Adipose tissue Increased Provide α-glycerol-3-PO4
Lipoprotein lipase
Lipolysis Decreased Hormone sensitive lipase
Ketogenesis Decreased HMG CoA synthetase
Lipoprotein Increased Utilization of VLDL & LDL

29. Protein Metabolism
Metabolism Net Effect Effect on important
enzymes
Protein Increased RNA polymerase
synthesis Amino acids up take
Protein Decreased Transaminases
degradation Deaminases

30. CELL GROWTH &
DEVELOPMENT
• Promote cell growth and development
• Mediated by
• Epidermal growth factors.
• Platelet derived growth factor.
• Prostaglandings.

31. CLINICAL CORRELATIONS

32. Symptoms of Diabetes
• Frequent urination
• Thirst
• Hunger
• Weight loss (despite thirst,
hunger)
• Fatigue
• Vision impairment

33. Continued…

34. Continued…

35. LEPRECHAUNISM

36. INSULINOMA
HYPERINSULINISM

37. Islet cell tumors, producing
such symptoms, are called
insulinomas

38. Insulin shock
High level of insulin.
Fall in blood glucose level.
CNS depression.
50-70 mg/dl CNS excitability
20-50 mg/dl CONVULSION&
COMA
< 20 mg/dl COMA

39. HYPOGLYCAEMIA IN FETUS
OF DIABETIC MOTHER
Maternal blood glucose level.
 Transfered through placenta.
Fetal blood glucose level.
o β-cells of fetus secrete insulin.
o Saturation of placenta 30 mmol/L
o Hypoglycaemia

40. REFERENCES
• Lectures on “Endocrinology” by C.J.Baired
MD/PhD
• www.dtu.ox.ac.uk/4-T
• Lectures on “Signaling Through Insulin
Receptors” by Oksana Matveinko
• Wikipedia
• Arthur C.Guyton, John E.Hall, “Textbook Of
Medical Physiology” 11th edition Ch: 78
Page:961-970
• Lectures By MA Hussain & ND Theise “ Stem-Cell
Therapy For Diabetes Mellitus”

41. Contd.
• Robert K.Murray, Daryl K.Granner, Victor
W.Rodwell, “Harper’s Illustrated Biochemistry” 27TH
edition Ch:41 Page: 457
• John T.Hensen, Bruce M.Koeppen, “Netter’s Atlas
Of Physiology” 5th edition Ch:8 Fig. 8.19,8.20
• Robert B.Dunn “Kaplan Medical Physiology USMLE
Step 1 Lecture Notes” Section:9 Ch: 5 Page:
407-413
• Insulin by Dr. Dana Armstrong and
Dr. Allen Bennett King

42. Acknowledgements
• Almighty Allah for giving me
audacity for my each step to its triumphant
completion
My Parents
Head of Biochemistry Department
Dr. Shafqat Nazir
All teachers of biochemistry department
My Friends
Library staff
Projectionist

43. 43