Insulin improves postischemic recovery of function through PI3K in isolated working rat heart

Vlad Zaha, Ieda Francischetti, Torsten Doesnt

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)229-232
Number of pages4
JournalMolecular and Cellular Biochemistry
Volume247
Issue number1-2
DOIs
StatePublished - May 1 2003

Keywords

  • Glucose uptake
  • Insulin
  • Myocardial ischemia
  • Phosphatidyl inositol 3-kinase
  • Reperfusion

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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