1. By Dr. Beenish Zaki Senior Instructor Department of Biochemistry
Insulin
By Dr. Beenish Zaki
Senior Instructor Department of Biochemistry

2. Objectives Insulin structure, synthesis, secretion. Insulin receptor.
GLUT transporters.
Mechanism of insulin action. Degradation. Regulation.
Clinical manifestations of DKA

3. Insulin structure Insulin is protein in nature.
It has Two polypeptide chains.
A Chain has 21 amino acid
B chain has 30 amino acid
Held together by disulphide bonds.

4. Difference between various Insulin
The Insulin can be derived from animal sources such as cow, pig.
The difference is in the B chain at 30th Amino acid.
Human being has Threonine
Bovine and pig have Alanine

5. Insulin
Produced by the Beta Cell of Islet cell of Langerhans in Pancreas

6. Synthesis of Insulin
Insulin is made as Pre Pro Insulin in the ribosomes. The leader stand is cleaved by proteases in the cell leading to stable ProInsulin.
ProInsulin is stored in the beta cells of Pancreas. ProInsulin is a single polypeptide chain with 86 amino acids.
Active Insulin has missing connecting peptide also know as C-peptide which is released in circulation.

7. How do we sense high blood sugar and release Insulin?
The beta cells are permeable to glucose.
The glucose is phosphorylated through Glucokinase.
Increasing blood glucose causes increase in glycolysis, TCA and generation of ATP.
Increased ATP generation inhibits ATP-sensitive K+ Channel causing membrane depolarization of cell membrane.
This causes Increase of Calcium stimulating exocytosis of Insulin.

8. Insulin Release

9. Glucose Transport from Lumen to Intestinal Cell

10. SGLuT-1 Transporters
Glucose has specific transporters which are trans membrane proteins.
Glucose Transport from Lumen to Intestinal cells happens because of SGLuT-1 by secondary active transport

11. Release of Glucose from Intestine to Blood

12. SGLuT
The same intestinal cells have a different transport mechanism facing capillaries.
They release glucose to blood stream by mechanism called Glucose transporter type (GluT 2)
This transporter is not dependent on sodium.
It is a uniport facilitated diffusion system.

13. GLUT 2 In Kidney

14. Glucose Transporter 4
Major transporter in skeletal muscles and adipose tissues.
Called GLUT 4
Under control of Insulin
Insulin induces the movement of GLUT4 molecules to the cell surface and Increases Glucose uptake.

15. GLuT 4 Mechanism

16. Glucose Transporters Tissue Location Function
Facilitative bidirectional transporters
GLUT 1
Brain, Kidney, Colon, erythrocytes
Glucose uptake
GLUT 2
Liver, pancreatic beta cell, small intestine and kidney
Rapid uptake or release of Glucose
GLUT 3
Brain and Kidney
GLUT 4
Heart and skeletal muscle, adipose tissue
Insulin-stimulated glucose uptake
GLUT 5
Small intestine
Absorption of gluocse

17. Glucagon
Produced by the Alpha Cell of Islet cell of Langerhans in Pancreas

18. Tissue response to Insulin and Glucagon
Liver
Adipose TissueGlu
Muscle
Increased by Insulin
Fatty acid synthesis
Glycogen synthesis
Protein synthesis
Glucose uptake
Decreased by Insulin
Ketogenesis
Gluconeogenesis
Lipolysis
Increased by Glucagon
Glycogenolysis

19. Glucagon opposes the action of Insulin
Secretion is stimulated by hypoglycemia
Effects only the liver.
Has no effect on muscle phosphorylase.
Acts by causing hyperglycemia through glycogenolysis and gluconeogenesis.

20. DKA