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

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

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.

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

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

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.

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.

Insulin Release

Glucose Transport from Lumen to Intestinal Cell

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

Release of Glucose from Intestine to Blood

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.

GLUT 2 In Kidney

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.

GLuT 4 Mechanism

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

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

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

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.

DKA