Role of Insulin in Health and Disease: a polypeptide hormone.

1.Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas.
2.Insulin, a hormone composed of 51 amino acids, plays important roles in glucose homeostasis, cell growth, and metabolism. The A chain comprises 21 amino acids and the B chain 30 amino acids. The A chain has an N-terminal helix linked to an anti-parallel C-terminal helix; the B chain has a central helical segment. The two chains are joined by 2 disulphide bonds, which join the N- and C-terminal helices of the A chain to the central helix of the B chain. In pro-insulin, a connecting peptide links the N-terminus of the A chain to the C-terminus of the B chain
3.The human pancreas contains one to two million pancreatic islets housing different endocrine cells, primarily insulin-secreting β cells, glucagon-producing α cells, and somatostatin-secreting δ cells.
4.The phosphorylation of glucose by the enzyme glucokinase (GCK) is the first step in glucose metabolism. Glucose phosphorylation by GCK is related to insulin secretion; therefore, GCK gene dysfunction or aberration leads to decreased glucose-mediated insulin release and glucose intolerance or diabetes.
5.After being secreted from pancreatic β cells and circulating through the body, insulin binds to insulin receptors (IRs) on target cell membranes. This results in the phosphorylation of insulin receptor substrate (IRS) and the subsequent activation of two primary signaling pathways, viz. the phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) pathway and the mitogen-activated protein kinase (MAPK) pathway.
6. The major purpose of insulin is to regulate the body’s energy supply by balancing micronutrient levels during the fed state. Insulin is critical for transporting intracellular glucose to insulin-dependent cells/tissues, such as liver, muscle, and adipose tissue. Any imbalance in exogenous energy supplies results in the breakdown of fats stored in adipose tissue and eventually accelerates insulin secretion. In the following sections, we discuss the major role of insulin in regulating several insulin-dependent tissue/organ functions.
7.Major physiological roles of insulin in the liver, adipose tissue, and skeletal muscles. After production and release from pancreatic β cells, insulin enters the bloodstream to ultimately reach all other organs. In the liver, insulin helps promote the transport of glucose from the blood into hepatocytes, where it is further converted to glycogen, fatty acids, and triglycerides. In the skeletal muscles, insulin facilitates the uptake of glucose and amino acids from the bloodstream. The amino acids are subsequently used for functional protein synthesis, while glucose is mostly utilized in glycolysis to produce energy in the form of ATP. Glucose may also be converted to the glycogen that is mostly stored as energy for times of deficit. Insulin stimulates adipose tissue uptake of fatty acids, which are later converted into triglycerides.

1. Insulin Presented By- Ishwari Hemant Sidwadkar Mpharm 1 st Year Roll no. 2018 Subject-Advanced Pharmacology П Under The Guidance Of- Dr.N.S.Naikwade (Pro. & HOD. Of Pharmacology Department) Appasaheb Birnale college of pharmacy, sangali .

2. Contents Introduction Structure of insulin Biosynthesis Synthesis, packaging and release Regulation Actions of insulin Insulin receptor Mechanism of action Insulin preparations Reactions and drug interactions Uses of insulin Newer insulin delivery devices.

3. Histopathology of pancreas

4. Action of insulin

5. Mechanism of action There are two fundamental signal transducing pathway by which insulin act. Phosphotidylinositol-3 kinase or PI3- kinase pathway. Ras- MAP kinase pathway.

6. PI3 kinase Activates IRS by binding to it by phosphorylation. Then it phosphorylate PIP2 Forms PIP3 which act docking site for two kinases 1) PDK-1 2)Protein kinase B PDK-1 phosphorylates protein kinase B Which dissociates and move in cytoplasm Insertion of GLUT 4 receptor on membrane Causes effect on metabolism PI3- kinase pathway

7. Monomeric G- protein Ability to bind GDP and GTP for activation, IRS bind with adaptor protein GRB2 Bind and activates a guanine exchange factor protein SOS replace Ras GDP with GTP Activation of Ras lead to activation of kinase cascade- Raf , MEK Ultimately leads to activation of MAP kinase Translocate into nucleus Phosphorylation of many transcription factors Cell proliferation, diffferentiations . MAP kinase pathway

8. Reactions and drug interactions

9. Uses of insulin

10. Insulin resistance

11. Newer insulin delivery devices