TY - JOUR
T1 - Insulin improves postischemic recovery of function through PI3K in isolated working rat heart
AU - Zaha, Vlad
AU - Francischetti, Ieda
AU - Doesnt, Torsten
N1 - Funding Information:
This study was supported by a grant to T. Doenst from the German Research Foundation (Deutsche Forschungsgemein-schaft, Emmy Noether-Program, DO602/2). V. Zaha was the recipient of a research stipend from the State of Baden-Württemberg. We wish to thank Wilhelm Bone, Ph.D. for critically reviewing this manuscript and Vitalij Maks for technical assistance.
PY - 2003/5
Y1 - 2003/5
N2 - Insulin improves contractile function after ischemia, but does not increase glucose uptake in the isolated working rat heart. We tested the hypothesis that the positive inotropic effect of insulin is independent of the signaling pathway responsible for insulin-stimulated glucose uptake. We inhibited this pathway at the level of phosphatidyl inositol 3-kinase (PI3K) with wortmannin. Hearts were perfused for 70 min at physiological workload with Krebs-Henseleit buffer containing [2-3H] glucose (5 mM, 0.05 μCi/ml) and oleate (0.4 mM, 1% BSA) in the presence (WM, n = 5) or absence (control, n = 7) of wortmannin (WM, 3 μmol/ L). After 20 min, hearts were subjected to 15 min of total global ischemia followed by 35 min of reperfusion. Insulin (1 mU/ ml) was added at the beginning of reperfusion (WM + insulin n = 8, insulin n = 8). Cardiac power before ischemia was 8.1 ± 0.7 mW. Recovery of contractile function after ischemia was significantly increased in the presence of insulin (73.5 ± 8.9% vs. 38.5 ± 6.7%, p < 0.01). The addition of wortmannin completely abolished the effect of insulin on recovery (32.6 ± 6.4%). Glucose uptake was 1.84 ± 0.32 μmol/min/g dry before ischemia and was slightly elevated during reperfusion (2.68 ± 0.35 μmol/ min/g dry, n.s.). Insulin did not affect postischemic glucose uptake. In the presence of wortmannin, glucose uptake was lowest during reperfusion (n.s.). The results suggest that PI3K is involved in the insulin-induced improvement in postischemic recovery of contractile function. This effect of insulin is independent of its effect on glucose uptake.
AB - Insulin improves contractile function after ischemia, but does not increase glucose uptake in the isolated working rat heart. We tested the hypothesis that the positive inotropic effect of insulin is independent of the signaling pathway responsible for insulin-stimulated glucose uptake. We inhibited this pathway at the level of phosphatidyl inositol 3-kinase (PI3K) with wortmannin. Hearts were perfused for 70 min at physiological workload with Krebs-Henseleit buffer containing [2-3H] glucose (5 mM, 0.05 μCi/ml) and oleate (0.4 mM, 1% BSA) in the presence (WM, n = 5) or absence (control, n = 7) of wortmannin (WM, 3 μmol/ L). After 20 min, hearts were subjected to 15 min of total global ischemia followed by 35 min of reperfusion. Insulin (1 mU/ ml) was added at the beginning of reperfusion (WM + insulin n = 8, insulin n = 8). Cardiac power before ischemia was 8.1 ± 0.7 mW. Recovery of contractile function after ischemia was significantly increased in the presence of insulin (73.5 ± 8.9% vs. 38.5 ± 6.7%, p < 0.01). The addition of wortmannin completely abolished the effect of insulin on recovery (32.6 ± 6.4%). Glucose uptake was 1.84 ± 0.32 μmol/min/g dry before ischemia and was slightly elevated during reperfusion (2.68 ± 0.35 μmol/ min/g dry, n.s.). Insulin did not affect postischemic glucose uptake. In the presence of wortmannin, glucose uptake was lowest during reperfusion (n.s.). The results suggest that PI3K is involved in the insulin-induced improvement in postischemic recovery of contractile function. This effect of insulin is independent of its effect on glucose uptake.
KW - Glucose uptake
KW - Insulin
KW - Myocardial ischemia
KW - Phosphatidyl inositol 3-kinase
KW - Reperfusion
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U2 - 10.1023/A:1024183527668
DO - 10.1023/A:1024183527668
M3 - Article
C2 - 12841653
AN - SCOPUS:0038080921
SN - 0300-8177
VL - 247
SP - 229
EP - 232
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -