Mechanism of insulin action

Abstract

Insulin acts on target cells via membrane-bound tetrameric receptors with tyrosine kinase activity. Binding of insulin to extracellular α-subunits of insulin receptor (IR) leads to autophosphorylation followed by increased tyrosine kinase activity in the cytoplasmic β-subunits of IR. Increased tyrosine kinase activity of IR phosphorylates and activates a protein called insulin receptor substrate-1 (IRS-1). Then activated IRS-1 interacts with a number of signalling proteins and transmits insulin signal through various signal transduction pathways. Activation of PI3-kinase by IRS-1 results in translocation of glucose transporters (GLUT 4) to the cell membrane and increased glucose influx. IRS-1 also activates p21ras via GRB2. Insulin action via P21ras-MAPK-pp90 S6 kinase alters nuclear events and glycogenesis. Insulin-activated IR and IRS-1 also interact with several other signalling proteins. However, the details of insulin action via these proteins and resultant biological effects remain to be investigated.