Cardiac-selective GLUT4 deficiency in fasted mice resulted in depressed glucose utilization, profound systolic and diastolic dysfunction, and accelerated ATP depletion during ischemia.
Mice with cardiac-selective GLUT4 deficiency subjected to global low-flow ischemia to determine the role of GLUT4 in mediating glycolytic flux.
Cardiac-selective GLUT4 deficiency vs Normal GLUT4 function / Fed state vs 20-hour fast
Glucose utilization, systolic and diastolic dysfunction, and ATP depletion during ischemia
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. METHODS AND 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.
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Rong Tian
Heart Failure & Transplant
E. Dale Abel
General Cardiology
Circulation
Brigham and Women's Hospital
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Tian et al. (Tue,) conducted a other in Myocardial ischemia. Cardiac-selective GLUT4 deficiency vs. Normal GLUT4 function / Fed state vs 20-hour fast was evaluated on Glucose utilization, systolic and diastolic dysfunction, and ATP depletion during ischemia. Cardiac-selective GLUT4 deficiency in fasted mice resulted in depressed glucose utilization, profound systolic and diastolic dysfunction, and accelerated ATP depletion during ischemia.
synapsesocial.com/papers/6a229a65cce2ba38c0cd4287 — DOI: https://doi.org/10.1161/01.cir.103.24.2961
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