Sign-up for our newsletter

Publication

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
Name Institution E. Dale Abel University of Iowa Adam Wende University of Alabama at Birmingham

Complications
All ComplicationsBioinformatics BoneCardiomyopathy CardiovascularGastro-Intestinal (GI) NephropathyNeuropathy & Neurocognition Pediatric Endocrinology Retinopathy UropathyWound Healing