Journal article
Absence of glucose transporter 4 diminishes electrical activity of mouse hearts during hypoxia
Experimental physiology, Vol.98(3), pp.746-757
03/2013
DOI: 10.1113/expphysiol.2012.070235
PMCID: PMC6599691
PMID: 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 (V
es
) from the epicardium of isolated, perfused mouse hearts. The normalized average of the maximal downstroke of V
es
(|dV
es
/d
t
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/d
t
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
V
es/d
t
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.
Details
- Title: Subtitle
- Absence of glucose transporter 4 diminishes electrical activity of mouse hearts during hypoxia
- Creators
- Kwanghyun Sohn - Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USAAdam R Wende - School of Medicine, Division of Endocrinology, Metabolism and Diabetes, Program in Molecular Medicine, University of Utah, Salt Lake City, UT, USAE. Dale Abel - School of Medicine, Division of Endocrinology, Metabolism and Diabetes, Program in Molecular Medicine, University of Utah, Salt Lake City, UT, USAAlonso P Moreno - Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USAFrank B Sachse - Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USABonnie B Punske - Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA
- Resource Type
- Journal article
- Publication Details
- Experimental physiology, Vol.98(3), pp.746-757
- DOI
- 10.1113/expphysiol.2012.070235
- PMID
- 23180812
- PMCID
- PMC6599691
- ISSN
- 0958-0670
- eISSN
- 1469-445X
- Language
- English
- Date published
- 03/2013
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024529302771
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