GLUT1 deficiency in cardiomyocytes does not accelerate the transition from
compensated hypertrophy to heart failure.
Authors Pereira RO, Wende AR, Olsen C, Soto J, Rawlings T, Zhu Y, Riehle C, Abel ED
Submitted By E. Dale Abel on 4/15/2014
Status Published
Journal Journal of molecular and cellular cardiology
Year 2014
Date Published 2/25/2014
Volume : Pages 72C : 95 - 103
PubMed Reference 24583251
Abstract The aim of this study was to determine whether endogenous GLUT1 induction and
the increased glucose utilization that accompanies pressure overload hypertrophy
(POH) are required to maintain cardiac function during hemodynamic stress, and
to test the hypothesis that lack of GLUT1 will accelerate the transition to
heart failure. To determine the contribution of endogenous GLUT1 to the cardiac
adaptation to POH, male mice with cardiomyocyte-restricted deletion of the GLUT1
gene (G1KO) and their littermate controls (Cont) were subjected to transverse
aortic constriction (TAC). GLUT1 deficiency reduced glycolysis and glucose
oxidation by 50%, which was associated with a reciprocal increase in fatty acid
oxidation (FAO) relative to controls. Four weeks after TAC, glycolysis increased
and FAO decreased by 50% in controls, but were unchanged in G1KO hearts relative
to shams. G1KO and controls exhibited equivalent degrees of cardiac hypertrophy,
fibrosis, and capillary density loss after TAC. Following TAC, in vivo left
ventricular developed pressure was decreased in G1KO hearts relative to
controls, but+dP/dt was equivalently reduced in Cont and G1KO mice.
Mitochondrial function was equivalently impaired following TAC in both Cont and
G1KO hearts. GLUT1 deficiency in cardiomyocytes alters myocardial substrate
utilization, but does not substantially exacerbate pressure-overload induced
contractile dysfunction or accelerate the progression to heart failure.

Investigators with authorship
E. Dale AbelUniversity of Iowa