The aim of the study was to evaluate the impact of simulated acute hyperglycemia (HG) on PI3K/Akt signaling in preconditioned and non-preconditioned isolated rat hearts perfused with Krebs-Henseleit solution containing normal (11 mmol/l) or elevated (22 mmol/l) glucose subjected to ischemia-reperfusion. Ischemic preconditioning (IP) was induced by two 5-min cycles of coronary occlusion followed by 5-min reperfusion. Protein levels of Akt, phosphorylated (activated) Akt (P-Akt), as well as contents of BAX protein were assayed (Western blotting) in cytosolic fraction of myocardial tissue samples taken prior to and after 30-min global ischemia and 40-min reperfusion. In "normoglycemic" conditions (NG), IP significantly increased P-Akt at the end of long-term ischemia, while reperfusion led to its decrease together with the decline of BAX levels as compared to non-preconditioned hearts. On the contrary, under HG conditions, P-Akt tended to decline in IP-hearts after long-term ischemia, and it was significantly higher after reperfusion than in non-preconditioned controls. No significant influence of IP on BAX levels at the end of I/R was observed under HG conditions. It seems that high glucose may influence IP-induced activation of Akt and its downstream targets, as well as maintain persistent Akt activity that may be detrimental for the heart under above conditions.

Institute for Heart Research Slovak Academy of Science Bratislava Slovak Republic

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