Discrepancy between GLUT4 translocation and glucose uptake after ischemia |
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Authors: | Vlad Zaha Roland Nitschke Heike Göbel Ulrich Fischer-Rasokat Christoph Zechner Torsten Doenst |
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Institution: | (1) Department of Cardiovascular Surgery, Albert-Ludwigs-University of Freiburg, Freiburg, Germany;(2) Life Imaging Center, Institute of Biology I, Albert-Ludwigs-University of Freiburg, Freiburg, Germany;(3) Institute of Pathology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany;(4) Department of Cardiovascular Surgery, University of Freiburg, Hugstetter Street 55, 79106 Freiburg i. Br., Germany |
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Abstract: | Objective: Low-flow ischemia results in glucose transporter translocation and in increased glucose uptake. After total ischemia in
rat heart, we found no increase in glucose uptake. Here we test the hypothesis that total ischemia is associated with decreased
activation of GLUT4 despite translocation. Methods: Isolated working hearts (n=70, Sprague–Dawley rats) were perfused for 70 min at physiological workload with Krebs–Henseleit buffer containing 2-3H]glucose (5 mmol/l, 0.05 μCi/ml) with either oleate (0.4 mmol/l, 1%BSA) or pyruvate (5 mmol/l, 1%BSA). After 20 min, hearts
were subjected to 15 min of total ischemia followed by 35 min of reperfusion. We measured glucose uptake and intracellular
free glucose (IFG) using 2-3H]glucose and 14C]sucrose, and determined the distribution of GLUT4 by colocalization immunofluorescence with Na–K ATP-ase. Results: Cardiac power was 10.1 ± 0.90 mW before ischemia and did not differ between groups. Recovery was the same in both groups
(55.7 ± 24.8$%). Glucose uptake did not differ between groups before ischemia, and did not increase during reperfusion. Despite
evidence of GLUT4 translocation after reperfusion in both groups, IFG did not increase compared with before ischemia. Conclusion: We conclude that there is a discrepancy between glucose transporter availability and glucose uptake after ischemia, which
may be due to inhibition of GLUT4 in the plasma membrane. (Mol Cell Biochem 278: 129–137, 2005) |
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Keywords: | insulin ischemia signal transduction |
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