Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes

Abstract

Background: Acute myocardial ischemia is accompanied by an increase in glucose uptake and metabolism, which appears to be important in protecting myocardial cells from irreversible ischemic injury. Because insulin 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 hearts and determined the expression of the major myocardial glucose transporter, GLUT4, in these separated membrane fractions. We found that translocation of GLUT4 molecules occurred in ischemic, hypoxic, and insulin-treated hearts and in hearts that underwent ischemia plus insulin treatment. The percentages of GLUT4 molecules present on the plasma membrane 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 significant differences in these values were the difference between control and ischemia and the difference between ischemia alone and insulin plus ischemia. Conclusions: Ischemia causes substantial translocation of GLUT4 molecules to the plasma membrane of cardiac myocytes. A combination 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 mechanism for the cardioprotective effect of insulin during acute myocardial ischemia.