TY - JOUR
T1 - Discrepancy between GLUT4 translocation and glucose uptake after ischemia
AU - Zaha, Vlad
AU - Nitschke, Roland
AU - Göbel, Heike
AU - Fischer-Rasokat, Ulrich
AU - Zechner, Christoph
AU - Doenst, Torsten
N1 - Funding Information:
T. D. was supported by the German Research Foundation (Emmy Noether Program, Do602/2-1 and 2-2). V. Z. was the recipient of a research stipend from the State of Baden-Württemberg. We would like to thank Lieselotte Bokla, Sabine Haxelmans and Vitalij Maks for technical assistance. We also wish to thank E. Dale Abel M.D., D.Phil. for many helpful comments and suggestions.
PY - 2005/10
Y1 - 2005/10
N2 - 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 = 7 0, 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.
AB - 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 = 7 0, 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.
KW - Insulin
KW - Ischemia
KW - Signal transduction
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U2 - 10.1007/s11010-005-7154-2
DO - 10.1007/s11010-005-7154-2
M3 - Article
C2 - 16180098
AN - SCOPUS:26444547652
SN - 0300-8177
VL - 278
SP - 129
EP - 137
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -