Mobilization of GLUT4 from intracellular vesicles by insulin and K 1 depolarization in cultured H 9 c 2 myotubes

Yu, Bo, Laurie A. Poirier, and Laura E. Nagy. Mobilization of GLUT-4 from intracellular vesicles by insulin and K1 depolarization in cultured H9c2 myotubes. Am. J. Physiol. 277 (Endocrinol. Metab. 40): E259–E267, 1999.—The insulinresponsive glucose transporter, GLUT-4, moves from an intracellular compartment to the cell surface in response to insulin and/or muscle contraction. Treatment of H9c2 myotubes with insulin significantly increased uptake of 2-deoxyglucose. Depolarization of the myotubes by increasing extracellular [K1], which mimics the initial phases of excitation-contraction coupling, also increased 2-deoxyglucose uptake. The K1but not insulin-evoked increase was blocked by dantrolene, an inhibitor of Ca21 release from the sarcoplasmic reticulum. In contrast, wortmannin, an inhibitor of phosphatidylinositol 3-kinase, blocked insulinbut not K1-stimulated 2-deoxyglucose uptake. Increased glucose uptake in response to insulin or K1 depolarization was associated with increased GLUT-4 in plasma membranes and depletion of a population of small intracellular GLUT-4-containing vesicles. Similarly, in H9c2 cells transfected with c-myc-tagged GLUT-4, translocation of c-myc GLUT-4 to the cell surface was increased after stimulation with insulin or K1 depolarization. Taken together, these data demonstrate that insulin and K1 depolarization increase glucose uptake by recruiting GLUT-4 from intracellular vesicles to the plasma membrane of H9c2 myotubes via distinct signaling mechanisms.