Insulin and its mechanism of action

Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides.

1. INSULIN AND ITS MECHANISM OF ACTION INSULIN AND ITS MECHANISM OF ACTION -Ashmita Chaudhuri B.Pharm, 4 th year, 7 th semester Roll- 27701910050 NSHM College Of Pharmaceutical Technology

2. INTRODUCTION: Insulin is a peptide hormone , produced by beta cells of the pancreas , and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver , skeletal muscles , and fat tissue to absorb glucose from the blood . In the liver and skeletal muscles, glucose is stored as glycogen , and in fat cells ( adipocytes ) it is stored as triglycerides . When control of insulin levels fails, diabetes mellitus can result. As a consequence, insulin is used medically to treat some forms of diabetes mellitus.

3. STRUCTURE OF INSULIN Human insulin consists of 51aa in two chains connected by 2 disulfide bridges (a single gene product cleaved into 2 chains during post-translational modification). T 1/2 ~5-10 minutes, degraded by glutathione-insulin transhydrogenase (insulinase) which cleaves the disulfide links. Bovine insulin differs by 3aa, pork insulin differs by 1aa. Insulin is stored in a complex with Zn 2+ ions.

4. BIOSYNTHESIS OF INSULIN:

5. REGULATION OF INSULIN: The endogenous production of insulin is regulated in several steps along the synthesis pathway: At transcription from the insulin gene In mRNA stability At the mRNA translation In the post translational modifications

6. EFFECT OF INSULIN ON GLUCOSE UPTAKE AND METABOLISM

7. MECHANISM OF ACTION: Insulin acts on specific receptors located on the cell membrane of practically every cell, but their density depends on the cell type: liver and fat cells are very rich. The insulin receptor is a receptor tyrosine kinase (RTK) which is a heterotetrameric glycoprotein consisting of 2 extracellular α and 2 transmembrane β subunits linked together by disulfide bonds, orienting across the cell membrane as a heterodimer It is oriented across the cell membrane as a heterodimer. The α subunits carry insulin binding sites, while the β subunits have tyrosine kinase activity.

8. MECHANISM OF ACTION: Insulin stimulates glucose transport across cell membrane by ATP dependent translocation of glucose transporter GLUT4 to the plasma membrane. The second messenger PIP 3 and certain tyrosine phosphorylated guanine nucleotide exchange proteins play crucial roles in the insulin sensitive translocation of GLUT4 from cytosol to the plasma membrane, especially in the skeletal muscles and adipose tissue. Over a period of time insulin also promotes expression of the genes directing synthesis of GLUT4. Genes for a large number of enzymes and carriers are regulated by insulin through Ras/Raf and MAP-Kinase as well as through the phosphorylation cascade.

9. DEGRADATION OF INSULIN: The internalized receptor-insulin complex is either degraded intercellularly or returned back to the surface from where the insulin is released extracellularly. The relative preponderance of these two processes differs among different tissues: maximum degradation occurs in liver, least in vascular endothelium.

10. FATE OF INSULIN Insulin is distributed only extracellularly. It is a peptide; gets degraded in the g.i.t. if given orally. Injected insulin or that released from the pancreas is metabolized primarily in liver and to a smaller extent in kidney and muscles. Nearly half of the insulin entering portal vein from pancreas is inactivated in the first passage through liver. Thus, normally liver is exposed to a much higher concentration (4-8 fold) of insulin than other tissues. During biotransformation the disulfide bonds are reduced- A and B chains are separated. These are further broken down to the constituent amino acids. The plasma t 1/2 is 5-9 minutes.

11. Different types of Insulin Preparations: Type Appearance Onset (hr) Peak (hr) Duration (hr) RAPID ACTING Insulin lispro Clear 0.2-0.3 1-1.5 3-5 Insulin aspart Clear 0.2-0.3 1-1.5 3-5 Insulin glulisin Clear 0.2-0.4 1-2 3-5 SHORT ACTING Regular (soluble) insulin Clear 0.5-1 2-3 6-8 INTERMEDIATE ACTING Insulin zinc suspension or Lente Cloudy 1-2 8-10 20-24 NPH or isophane Insulin Cloudy 1-2 8-10 20-24 LONG ACTING Insulin glargine and Insulin detemir Clear Glargine: 2-4 Detemir: 1-4 _ _ Glargine: 24 Detemir: 20-24

12. CONCLUSION:

13. REFERENCES: http://edrv.endojournals.org/content/2/2/210.abstract visited on 10 th October, 2013. http:// en.wikipedia.org/wiki/Insulin visited on 25 th September, 2013 http://www.authorstream.com/Presentation/saneet-1638200-insulin-inside/ visited on 28 th September, 2013 . http://www.google.co.in/url?sa=t&rct=j&q=& esrc=s&source=web&cd=1&ved=0CC8QFjAA&url=http%3A%2F%2Fwww.calstatela.edu%2Ffaculty%2Fmchen%2F454L%2520lectures%2FAntiDiabeticDrugs.ppt&ei=wzV_UsryE8isrAfXsIH4Bg&usg=AFQjCNGP7mDC39_aOTodF7_SYzObBpFcPQ visited on 20 th October, 2013. http://www.medbio.info/horn/time%203-4/homeostasis_2.htm visited on 2 nd November, 2013. Essentials of Medical Pharmacology- by KD Tripathi, 7 th Edition, Jaypee Brothers Medical Publishers (P) Limited, Chapter-19, Page: 258-268.