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. 2013 Mar;98(3):746-57.
doi: 10.1113/expphysiol.2012.070235. Epub 2012 Nov 23.

Absence of glucose transporter 4 diminishes electrical activity of mouse hearts during hypoxia

Kwanghyun Sohn  1 , Adam R Wende, E Dale Abel, Alonso P Moreno, Frank B Sachse, Bonnie B Punske
Affiliations

Absence of glucose transporter 4 diminishes electrical activity of mouse hearts during hypoxia

Kwanghyun Sohn et al. Exp Physiol. 2013 Mar.

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.

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Figures

Figure 1.
Figure 1.. Cylindrical 64-electrode array
A, photograph of the electrode array. B, the triangulated mesh geometry of the electrode array in three dimensions. The electrode array formed a cylinder 8.03 mm in diameter and 5.16 mm in length. C, two-dimensional triangulated mesh of the electrode array with electrode numbers. Five electrodes were arranged in each column with 1.29 mm interelectrode distance, and 13 columns were arranged circumferentially with 1.94 mm interelectrode spacing.
Figure 2.
Figure 2.
Typical examples of recorded potentials with |dVes/dtmin (magnitude of the maximum downstroke of the surface potentials) marked by tangential lines and| values indicated (in volts per second) during baseline conditions, during hypoxia and during reoxygenation for each cohort
Figure 3.
Figure 3.
Mean values and standard error of |dVes/dtmin na(normalized average of the magnitude of the maximum | downstroke of the surface potentials) as a function of time during hypoxia for each cohort Times are as follows: 0–30 min, baseline; 30–60 min, hypoxia; and 60–90 min, reoxygenation.
Figure 4.
Figure 4.. Activation time maps for selected hearts during hypoxia
For each set of experimental conditions, activation time maps are displayed at the end of baseline (30 min), at the end of hypoxia (60 min) and at the end of reoxygenation (90 min). The total activation time (TAT) and correlation coefficient of action potential propagation sequences (Cas) are also listed above the corresponding activation time map. The electrode positions as shown in Fig. 1C are overlaid on the first map in A. White indicates early activation and black indicates late activation.
Figure 5.
Figure 5.
Values of |dVes/dtmin|na (A), Cas (B), TATn (C) and normalized heart rate (HRn) (D) at the end of hypoxia (60 min) and at the end of reoxygenation (90 min) *P < 0.05 for G4H−/− versus CTL. +P < 0.05 for with versus without insulin.
Figure 6.
Figure 6.
Values of |dVes/dtmin|na (A), Cas (B), TATn (C) and HRn (D) at the end of glucose withdrawal (60 min) and at the end of glucose resupply (90 min) *P < 0.05 versus corresponding CTL.
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References

    1. Abel ED (2004). Glucose transport in the heart. Front Biosci 9,201–215. - PubMed
    1. Abel ED (2005). Myocardial insulin resistance and cardiac complications of diabetes. Curr Drug Targets Immune Endocr Metabol Disord 5, 219–226. - PubMed
    1. Abel ED, Kaulbach HC, Tian R, Hopkins JC, Duffy J,Doetschman T, Minnemann T, Boers ME, Hadro E, Oberste-Berghaus C, Quist W, Lowell BB, Ingwall JS & Kahn BB (1999). Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest 104, 1703–1714. - PMC - PubMed
    1. Arya DS, Bansal P, Ojha SK, Nandave M, Mohanty I & Gupta SK (2006). Pyruvate provides cardioprotection in the experimental model of myocardial ischemic reperfusion injury. Life Sci 79, 38–44. - PubMed
    1. Aulbach F, Simm A, Maier S, Langenfeld H, Walter U, Kersting U & Kirstein M (1999). Insulin stimulates the L-type Ca2+current in rat cardiac myocytes. Cardiovasc Res 42, 113–120. - PubMed

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