Molecular basis for insulin-stimulated GLUT4 translocation

In muscle and adipose tissues, the clearance of circulating glucose depends upon the insulin-stimulated translocation of the glucose transporter GLUT4 isoform from its intracellular compartment(s) to the cell surface. This translocation process involves four basic steps, beginning with the activation of the intrinsic tyrosine kinase activity of the insulin receptor: The stimulation of complex sets of effector molecules generating various signaling cascades, the movement/trafficking of intracellular GLUT4 storage compartments toward the plasma membrane, docking of these compartments with the cell surface membrane, and the ultimate fusion of these compartments with the plasma membrane allowing the facilitative entry of glucose into the cell. Although these four stages of GLUT4 translocation are generally well accepted, the molecular details and specific proteins involved in these discreet events have remained highly elusive. Advances have recently been made in identifying new signaling pathways and effector proteins that may link signaling to the activation of vesicle trafficking.