Glucose transport is the rate-limiting step for glucose utilization in muscle. In muscle and adipose tissue, glucose transport is acutely regulated by such factors as insulin and exercise. Translocation of glucose transporters (GLUT4) from an intracellular domain to the cell surface is the major mechanism for this regulation. Using immunocytochemistry, the intracellular distribution of GLUT4 under resting conditions is similar in adipocytes and myocytes. GLUT4 is concentrated in tubulovesicular structures either in the trans-Golgi region or in the cytosol, often close to the cell surface but not on the cell surface. After stimulation, cell surface GLUT4 labeling is increased by as much as 40-fold.
GLUT4 is chronically regulated by altered gene expression. Neural and/or contractile activity regulates GLUT4 expression in muscle: 1) GLUT4 levels differ among muscles of different fiber type; 2) GLUT4 levels in muscle are increased with exercise training and decreased with denervation; and 3) cultured muscle cells, which lack an intact nerve supply, express very low levels of GLUT4. GLUT4 expression appears to be regulated in parallel with many oxidative enzymes in muscle, suggesting that there may be a unified developmental program that determines the overall metabolic properties of a particular muscle. Preliminary evidence suggests that impaired GLUT4 expression in muscle is not the primary defect associated with insulin resistance. Nevertheless, it is conceivable that the adaptive increase in muscle GLUT4 that is found with exercise training may have beneficial effects in insulin-resistant states such as non-insulin-dependent diabetes.
