Mobilization of GLUT-4 from intracellular vesicles by insulin and K(+) depolarization in cultured H9c2 myotubes.
The insulin-responsive 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 [K(+)], which mimics the initial phases of excitation-contraction coupling, also increased 2-deoxyglucose uptake. The K(+)- but not insulin-evoked increase was blocked by dantrolene, an inhibitor of Ca(2+) release from the sarcoplasmic reticulum. In contrast, wortmannin, an inhibitor of phosphatidylinositol 3-kinase, blocked insulin- but not K(+)-stimulated 2-deoxyglucose uptake. Increased glucose uptake in response to insulin or K(+) 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 K(+) depolarization. Taken together, these data demonstrate that insulin and K(+) depolarization increase glucose uptake by recruiting GLUT-4 from intracellular vesicles to the plasma membrane of H9c2 myotubes via distinct signaling mechanisms.
Yu
B
B
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106-4906, USA.
Poirier
L A
LA
Nagy
L E
LE
D000730:Androstadienes / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003620:Dantrolene / Q000494:pharmacology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004357:Drug Synergism; D005110:Extracellular Space / Q000378:metabolism; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009132:Muscles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection; D000077191:Wortmannin
D000730:Androstadienes; D051275:Glucose Transporter Type 4; D007328:Insulin; D007329:Insulin Antagonists; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D003847:Deoxyglucose; D003620:Dantrolene; D011188:Potassium; D000077191:Wortmannin