THE GLUCOSE TRANSPORTERS OF SKELETAL-MUSCLE

Glucose transport into skeletal muscle occurs through the GLUT1 and GL UT4 glucose transporters. Muscle cells in culture also express the GLU T3 fetal muscle/neuronal type transporter. In skeletal muscle, the GLU T1 transporter is restricted to the cell surface, while the more abund ant GLUT4 transporter is largely sequestered intracellularly from wher e if is rapidly translocated to the cell surface in response to insuli n, exercise or hypoxia. The insulin effect has been documented by subc ellular fractionation of rat, mouse and human muscle, and has been con firmed quantitatively by photolabelling of the surface transporters an d qualitatively by immunoelectron microscopy. In L6 myotubes in cultur e, the GLUT1 and GLUT3 transporters are mostly located at the cell sur face but a fraction resides intracellularly, whereas the GLUT4 transpo rter is distributed evenly between the surface and the intracellular l ocation. Immunopurified intracellular GLUT4 vesicles from these cells do not contain appreciable amounts of GLUT1 or GLUT3 transporters, alt hough all three transporters respond to insulin by translocating to th e plasma membrane. The glucose transporter translocation induced by in sulin in skeletal muscle and L6 myotubes requires phosphatidylinositol 3-kinase activity, as does the maintenance of the basal amount of tra nsporters at the plasma membrane. Two different phosphatidylinositol 3 -kinase activities may control basal and insulin-dependent transport. In contrast, the stimulation of glucose transport induced by exercise or hypoxia is independent of this enzymatic activity. In both L6 myotu bes and mature skeletal muscle, the GLUT4-containing vesicle contains synaptobrevin II/VAMP-2 and cellubrevin. These proteins also redistrib ute in response to insulin, and may be required for correct vesicle do cking and/or fusion with the plasma membrane. (C) 1996 Academic Press Ltd