Role of insulin in human body

1. ROLE OF INSULIN
MARYAM JAMILAH BINTI ABDUL HAMID
082013100002
IMS BANGALORE

2. Learning outcome
• List down the role of insulin

3. Insulin
• It is a polypeptide hormone
• Made up of 51 amino acids
• Contains 2 chains: A and B
• A chain with 21 amino acids & B chain with 30
amino acids
• Has two types of disulphide bridges
– Intrachain disulphide bridge between A6 –A11
– Interchain disulphide bridges between A7 –B7 &
A20- B19

4. Insulin receptor
Target cell
α α
 
• It has two α & two  subunits, held
by disulphide bridges
• α subunits bind insulin
•  subunits
– have tyrosine kinase activity
(Kinase-phosphatase system, 2nd
messenger)
– Contain autophosphorylation sites

5. Target cell
Tyr- P Tyr- P
Insulin receptor
substrate -1 (IRS-1)
Insulin receptor
substrate -1 (IRS-1)
P
Cascade of protein phosphorylations & dephosphorylations by
kinases & phosphatases
Biological effects

6. Insulin bound to Insulin
receptor on target cell1
2
3
4
5
+
Glucose transported
inside by glucose
transporters
Stimulation for fusion of
internal vesicles containing
glucose transporters with the
target cell membrane
Endosome formation
Internalization
of glucose
transporters
when insulin
levels fall

7. Insulin bound to Insulin
receptor on target cell1
2
3
4
5
+
Glucose transported
inside by glucose
transporters
Stimulation for fusion of
internal vesicles containing
glucose transporters with the
target cell membrane
Endosome formation
Internalization
of glucose
transporters
when insulin
levels fall

8. Role of insulin
1. Uptake of glucose by
tissues
2. Utilization of glucose
3. Hypoglycemic effect
5. Lipogenesis
6. Anti-lipolytic effect
7. Anti-ketogenic effect
8. Other general effect

9. 1) Uptake of glucose by tissues
 Facilitates the membrane transport of glucose
 Enhanced facilitated diffusion of glucose in muscle
 In DM, GLUT 4 is reduced. However, glucose uptake
in liver (GLUT 2) is independent of insulin

10. 2) Utilization of glucose
• Stimulate glycolysis
• Key glycolytic enzymes
– Glucokinase
– Phosphofructokinase
– Pyruvate kinase
• Glycogen synthase is activated

11. 3) Hypoglycemic Effect
• Gluconeogenesis is inhibited
– Repress key enzyme (PC, PEPCK, G-6-phosphatase)
• Glycogenolysis is inhibited
– Inactivation of glycogen phosphorylase
– Inhibition of G-6-phosphatase

12. 4) Lipogenesis
• Favored
– Providing more acetyl CoA (from pyruvate
dehydrogenase reaction)
– Increase the activity of acetyl CoA carboxylase
– Provides NADPH by increasing the GPD activity of
the HMP shunt pathway

13. 5) Anti-lipolytic Effect
• Inhibits lipolysis in adipose tissue; inhibition of
hormone sensitive lipase
• Increased level of free FA in plasma in diabetes

14. 6) Anti-ketogenic Effect
• Depress HMG CoA synthase ( ketogenesis)
• Acetyl CoA – completely utilised in TCA cycle because
oxaloacetate is plenty.
• Favor fatty acid synthesis from acetyl CoA

15. 7) Other General Effect
• Promote protein synthesis & degradation is retarded
• An anabolic hormone
• Stimulate replication of cells; essential growth factor
in all mammalian cells

16. References
• Vasudevan, D., S, S., & Vaidyanathan, K.
(2013).Textbook of biochemistry for medical
students.New Delhi: Jaypee Brothers Medical
Publishers (P) Ltd.
• Dr Guruprasad Rao, Professor in
Biochemistry, MMMC, Manipal, India