Protection of ischemic hearts by high glucose is mediated, in part, by GLUT-4

Metabolic interventions that promote glucose use during ischemia have been shown to protect ischemic myocardium and improve functional recovery on rep erfusion. We evaluated whether the cardioprotection afforded by high glucos e during low-flow ischemia is associated with changes in the sarcolemmal co ntent of glucose transporters, specifically GLUT-4. Isolated rat hearts wer e paced at 300 beats/ min and perfused under normal glucose (5 mM) or high glucose (10 mM) conditions in buffer containing 0.4 mM albumin, 0.4 mM palm itate, and 70 mU/l insulin and subjected to 50 min of low-flow ischemia and 60 min of reperfusion. To determine the importance of insulin-sensitive gl ucose transporters in mediating cardioprotection, a separate group of heart s were perfused in the presence of cytochalasin B (10 muM), a preferential inhibitor of insulin-sensitive glucose transporters. Ischemic contracture d uring low-flow ischemia and creatine kinase release on reperfusion was decr eased, and the percent recovery of left ventricular function with reperfusi on was enhanced in hearts perfused with high glucose (P<0.03). Hearts perfu sed with high glucose exhibited increased GLUT-4 protein expression in the sarcolemmal membrane compared with control hearts under baseline conditions , and these changes were additive with low-flow ischemia. In addition, high glucose did not affect the baseline distribution of sarcolemmal GLUT-1 and blunted any changes with low-flow ischemia. These salutary effects were ab olished when glucose transporters are blocked with cytochalasin B. These da ta demonstrate that protection of ischemic myocardium by high glucose is as sociated with increased sarcolemmal content of the insulin-sensitive GLUT-4 and suggest a target for the protection of jeopardized myocardium.