Insulin-regulated membrane trafficking and whole body glucose homeostasis. One of the main acute effects of insulin is to regulate the disposal and storage of dietary glucose by stimulating the uptake of glucose into muscle and fat (Figure 1). Insulin regulates glucose uptake into these cells by recruiting membrane vesicles containing the GLUT4 glucose transporters from the interior of cells to the cell surface, where it allows glucose to enter cells by facultative diffusion. Once in the cytoplasm, the glucose is phosphorylated and thereby trapped inside cells. The effect of insulin on GLUT4 distribution is reversible. Within an hour of insulin removal, GLUT4 is removed from the membrane and restored intracellular in vesicles ready to be re-recruited to the surface by insulin. Thus, glucose uptake by muscle and fat cells is regulated by modulating the number of GLUT4 glucose transporters on the surface of cells.