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 reperfusion. We evaluated whether the cardioprotection afforded by high glucose during low-flow ischemia is associated with changes in the sarcolemmal content of glucose transporters, specifically GLUT-4. Isolated rat hearts were 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 palmitate, 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 glucose transporters in mediating cardioprotection, a separate group of hearts were perfused in the presence of cytochalasin B (10 microM), a preferential inhibitor of insulin-sensitive glucose transporters. Ischemic contracture during low-flow ischemia and creatine kinase release on reperfusion was decreased, and the percent recovery of left ventricular function with reperfusion was enhanced in hearts perfused with high glucose (P < 0.03). Hearts perfused 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 abolished when glucose transporters are blocked with cytochalasin B. These data demonstrate that protection of ischemic myocardium by high glucose is associated with increased sarcolemmal content of the insulin-sensitive GLUT-4 and suggest a target for the protection of jeopardized myocardium.
Ramasamy
R
R
Division of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. rr260@columbia.edu
Hwang
Y C
YC
Whang
J
J
Bergmann
S R
SR
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D003571:Cytochalasin B / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology* / Q000502:physiology; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism / Q000502:physiology*; D009124:Muscle Proteins; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D020011:Protective Agents; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D019344:Lactic Acid; D003571:Cytochalasin B; D003402:Creatine Kinase; D005947:Glucose