The glucose transporters of skeletal muscle

Glucose transport into skeletal muscle occurs through the GLUT1 and GLUT4 glucose transporters. Muscle cells in culture also express the GLUT3 fetal muscle/neuronal type transporter. In skeletal muscle, the GLUT1 transporter is restricted to the cell surface, while the more abundant GLUT4 transporter is largely sequestered intracellularly from where it is rapidly translocated to the cell surface in response to insulin, exercise or hypoxia. The insulin effect has been documented by subcellular fractionation of rat, mouse and human muscle, and has been confirmed quantitatively by photolabelling of the surface transporters and qualitatively by immunoelectron microscopy. In L6 myotubes in culture, the GLUT1 and GLUT3 transporters are mostly located at the cell surface but a fraction resides intracellularly, whereas the GLUT4 transporter is distributed evenly between the surface and the intracellular location. Immunopurified intracellular GLUT4 vesicles from these cells do not contain appreciable amounts of GLUT1 or GLUT3 transporters, although all three transporters respond to insulin by translocating to the plasma membrane. The glucose transporter translocation induced by insulin in skeletal muscle and L6 myotubes requires phosphatidylinositol 3-kinase activity, as does the maintenance of the basal amount of transporters 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 myotubes and mature skeletal muscle, the GLUT4-containing vesicle contains synaptobrevin II/VAMP-2 and cellubrevin. These proteins also redistribute in response to insulin, and may be required for correct vesicle docking and/or fusion with the plasma membrane.