Responses of GLUT4-deficient hearts to ischemia underscore the importance of
glycolysis.
Authors Tian R, Abel ED.
Submitted By E. Dale Abel on 3/8/2004
Status Published
Journal Circulation
Year 2001
Date Published 6/19/2001
Volume : Pages 103 : 2961 - 2966
PubMed Reference 11413087
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. 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.


Investigators with authorship
NameInstitution
E. Dale AbelUniversity of Iowa

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