ISCHEMIA INDUCES TRANSLOCATION OF THE INSULIN-RESPONSIVE GLUCOSE-TRANSPORTER GLUT4 TO THE PLASMA-MEMBRANE OF CARDIAC MYOCYTES

Background Acute myocardial ischemia is accompanied by an increase in glucose uptake and metabolism, which appears to be important in protec ting myocardial cells from irreversible ischemic injury. Because insul in augments myocardial glucose uptake by inducing the translocation of glucose transporters from an intracellular compartment to the plasma membrane, we hypothesized that acute ischemia would trigger a similar translocation. Methods and Results We used a subcellular fractionation method to separate intracellular membranes and plasma membranes from control, ischemic, and hypoxic Langendorff-isolated perfused rat heart s and determined the expression of the major myocardial glucose transp orter, GLUT4, in these separated membrane fractions. We found that tra nslocation of GLUT4 molecules occurred in ischemic, hypoxic, and insul in-treated hearts and in hearts that underwent ischemia plus insulin t reatment. The percentages of GLUT4 molecules present on the plasma mem brane in the different conditions were as follows: control, 18.0+/-2.8 %; ischemia, 41.3+/-9.4%; hypoxia, 31.1+/-2.9%; insulin, 61.1+/-2.6%; and ischemia plus insulin, 66.8+/-5.7%. Among the statistically signif icant differences in these values were the difference between control and ischemia and the difference between ischemia alone and insulin plu s ischemia. Conclusions Ischemia causes substantial translocation of G LUT4 molecules to the plasma membrane of cardiac myocytes. A combinati on of insulin plus ischemia stimulates an even greater degree of GLUT4 translocation. GLUT4 translocation is likely to mediate at least part of the increased glucose uptake of ischemic myocardium and may be a m echanism for the cardioprotective effect of insulin during acute myoca rdial ischemia.