Figure 3.

Control of glucose uptake by regulation of GLUT1 and GLUT4 endocytosis. Glucose transport from the extracellular milieu to the cytoplasm occurs selectively by glucose transporters (GLUTs) present at the cell surface. GLUT4 endocytosis occurs through both clathrin-mediated (CME) as well as clathrin-independent (CIE) endocytosis. The cell-surface content, and hence the rate of glucose uptake by GLUT1 and GLUT4, is regulated by alterations in the endocytosis of these glucose transporters, as well as the rates of recycling. Moreover, GLUT1 and GLUT4 undergo distinct intracellular sorting, with ∼50% of GLUT4 residing in a specialized storage compartment. Shown are some of the stimuli and intracellular signals that reduce the endocytosis of GLUT1 and GLUT4 or increase transporter recycling and thereby increase the rate of cellular glucose uptake. Also shown are the insulin-responsive aminopeptidase (IRAP) and VAMP2, which are enriched in the GLUT4 storage compartment and the transferrin receptor (Tfn rec.), which is not, and is instead found largely in recycling endosomes.