Mobilization of GLUT-4 from intracellular vesicles by insulin and K(+) depolarization in cultured H9c2 myotubes

Am J Physiol. 1999 Aug;277(2):E259-67. doi: 10.1152/ajpendo.1999.277.2.E259.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstadienes / pharmacology
  • Biological Transport / physiology
  • Cell Line
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Dantrolene / pharmacology
  • Deoxyglucose / pharmacokinetics
  • Drug Synergism
  • Extracellular Space / metabolism
  • Glucose Transporter Type 4
  • Insulin / pharmacology*
  • Insulin Antagonists / pharmacology
  • Intracellular Membranes / metabolism*
  • Monosaccharide Transport Proteins / metabolism*
  • Muscle Proteins*
  • Muscles / cytology
  • Muscles / drug effects*
  • Muscles / metabolism*
  • Potassium / antagonists & inhibitors
  • Potassium / metabolism
  • Potassium / pharmacology*
  • Transfection
  • Wortmannin


  • Androstadienes
  • Glucose Transporter Type 4
  • Insulin
  • Insulin Antagonists
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Deoxyglucose
  • Dantrolene
  • Potassium
  • Wortmannin