Outline the mechanism of insulin.

a) Insulin acts on specific receptor located on the cell membrane of practically every cell, but the density depends upon the cell type, liver and fat cells are very rich.

b) The insulin receptor is a receptor tyrosine kinase (RTK) which is a heterotetrametric glycoprotein consisting two extracellular alpha- and two transmembrane beta- subunits linked together by disulfide bonds, orienting across the cell membrane as a heterodimer.

c) The alpha -subunits carry insulin binding sites while beta-subunits have tyrosine kinase activity.

 STEPS:

1. IRS 1 phosphorylated by the insulin receptor activates PI3K by binding to its SH2 domain. PI3K converts PIP2 to PIP3 (PI3K is phospho-inositide 3 kinase).
2. PKB bound to PIP3 is phosphorylated by PDK-1. The activated PKB phosphorylates GSK3 on the serine residue, inactivating it.
3. The glycogen synthase kinase 3 (GSK3) is inactivated by phosphorylation, thus it cannot convert glycogen synthase (GS) to its inactive form by phosphorylation so GS remains active.
4. Synthesis of glycogen from glucose is accelerated rapidly in liver and muscles.
5. PKB stimulates movement of glucose transporter GLUT-4 from internal membrane vesicles to plasma membrane, thus increasing the uptake of glucose.