Regulated transport of the glucose transporter GLUT4

Following a meal, insulin secretion from the pancreas facilitates the removal of glucose from the bloodstream. One of the main events in this regulatory process is the stimulation of glucose entry into muscle and fat cells. This is mediated by the translocation of the facilitative glucose transporter GLUT4 from an intracellular store to the cell surface. The insulin-responsive GLUT4 is retained intracellularly in muscle and fat cells. In response to insulin, GLUT4 is translocated to the cell surface, where it facilitates the uptake of glucose into these insulin-responsive tissues. Understanding the transport itinerary of GLUT4 in these cells, both in the absence and presence of insulin, has proved to be a very challenging cell-biology problem. A model that we believe fits all of the available data available for GLUT4 transport at present is described. This model involves the intracellular cycling of GLUT4 between the trans-Golgi network, the endosomal system and the plasma membrane. The effect of insulin on this model is discussed in the article. Other potential models are also discussed. It is likely that the delivery of GLUT4 to the cell surface of fat and muscle cells is insufficient to account for the increase in glucose uptake into these cells, and therefore other layers of regulation, such as enhancement of transporter activity, might also be regulated by insulin. To understand how insulin leads to the translocation of GLUT4 to the cell surface of insulin-sensitive cells, it is necessary to identify a link between the insulin-signalling pathways and GLUT4 transport machinery.