title: Responses of GLUT4-deficient hearts to ischemia underscore the importance of glycolysis.
abstract: BACKGROUND
  The ischemic heart is dependent on glycolysis for ATP generation, and therapies that increase glucose utilization during ischemia improve survival. Myocardial ischemia results in the translocation of the glucose transporter proteins GLUT1 and GLUT4 to the sarcolemma. The increased glucose entry via these transporters contributes to enhanced glycolysis during ischemia.
  
  
  RESULTS
  To determine the role of GLUT4 in mediating increased glycolytic flux during ischemia, hearts from mice with cardiac-selective GLUT4 deficiency (G4H-/-) were subjected to global low-flow ischemia. During normal perfusion, hearts from fed G4H-/- mice showed increased GLUT1-mediated glucose uptake, higher concentrations of glycogen and phosphocreatine, but delayed recovery after ischemia. When these compensatory changes were eliminated by a 20-hour fast, G4H-/- hearts exhibited depressed glucose utilization during ischemia and developed profound and irreversible systolic and diastolic dysfunction associated with accelerated ATP depletion during ischemia and diminished regeneration of high-energy phosphate compounds on reperfusion.
  
  
  CONCLUSIONS
  GLUT4 is an important mediator of enhanced glycolysis during ischemia and represents an important protective mechanism against ischemic injury.
authors: NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: R
authors: R
authors: Tian
authors: E D
authors: ED
authors: Abel
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D003401:Creatine / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006321:Heart / Q000187:drug effects; D006339:Heart Rate; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D019344:Lactic Acid / Q000096:biosynthesis; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010710:Phosphates; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose; D003401:Creatine