Absence of glucose transporter 4 diminishes electrical activity of mouse hearts
during hypoxia.
Authors Sohn K, Wende AR, Abel ED, Moreno AP, Sachse FB, Punske BB
Submitted By Submitted Externally on 3/4/2015
Status Published
Journal Experimental physiology
Year 2013
Date Published 3/1/2013
Volume : Pages 98 : 746 - 757
PubMed Reference 23180812
Abstract Insulin resistance, which characterizes type 2 diabetes, is associated with
reduced translocation of glucose transporter 4 (GLUT4) to the plasma membrane
following insulin stimulation, and diabetic patients with insulin resistance
show a higher incidence of ischaemia, arrhythmias and sudden cardiac death. The
aim of this study was to examine whether GLUT4 deficiency leads to more severe
alterations in cardiac electrical activity during cardiac stress due to hypoxia.
To fulfil this aim, we compared cardiac electrical activity from
cardiac-selective GLUT4-ablated (G4H-/-) mouse hearts and corresponding control
(CTL) littermates. A custom-made cylindrical 'cage' electrode array measured
potentials (Ves) from the epicardium of isolated, perfused mouse hearts. The
normalized average of the maximal downstroke of Ves ( (|d Ves/dt(min)|na), which
we previously introduced as an index of electrical activity in normal, ischaemic
and hypoxic hearts, was used to assess the effects of GLUT4 deficiency on
electrical activity. The |d Ves/dt(min)|na of G4H -/- and CTL hearts decreased
by 75 and 47%, respectively (P < 0.05), 30 min after the onset of hypoxia.
Administration of insulin attenuated decreases in values of |d Ves/dt(min)|na in
G4H -/- hearts as well as in CTL hearts, during hypoxia. In general, however,
G4H -/- hearts showed a severe alteration of the propagation sequence and a
prolonged total activation time. Results of this study demonstrate that reduced
glucose availability associated with insulin resistance and a reduction in
GLUT4-mediated glucose transport impairs electrical activity during hypoxia, and
may contribute to cardiac vulnerability to arrhythmias in diabetic patients.

Investigators with authorship
E. Dale AbelUniversity of Iowa
Adam WendeUniversity of Alabama at Birmingham