Aim:Insulin exerts anti-apoptotic effects in both cardiomyocytes and coronaryendothelial cells following ischemia/reperfusion(I/R)via the Akt-endothelial ni-tric oxide synthase survival signal pathway.This important insulin signalingmight further contribute to the improvement of cardiac function after reperfusion.In this study,we tested the hypothesis that sarcoplasmic reticulum calcium-AT-Pase(SERCA2a)is involved in the insulin-induced improvement of cardiac con-tractile function following I/R.Methods:Ventricular myocytes were enzymaticallyisolated from adult SD rats.Simulated I/R was induced by perfusing cells withchemical anoxic solution for 15 min followed by reperfusion with Tyrode’s solu-tion with or without insulin for 30 min.Myocyte shortening and intracellularcalcium transients were assessed and underlying mechanisms were investigated.Results:Reperfusion with insulin(10~(-7)mol/L)significantly improved the recoveryof contractile function(n=15-20 myocytes from 6-8 hearts,P<0.05),and increasedcalcium transients,as evidenced by the increased calcium(Ca~(2+))fluorescenceratio,shortened time to peak Ca~(2+)and time to 50% diastolic Ca~(2+),compared withthose in cells reperfused with vehicle(P<0.05).In addition,Akt phosphorylationand SERCA2a activity were both increased in insulin-treated I/R cardiomyocytes,which were markedly inhibited by pretreatment of cells with a specific Akt inhibitor.Moreover,inhibition of Akt activity abolished insulin-induced positive contrac-tile and calcium transients responses in I/R cardiomyocytes.Conclusion:Thesedata demonstrated for the first time that insulin improves the recovery of contrac-tile function in simulated I/R cardiomyocytes in an Akt-dependent and SERCA2a-mediated fashion. Aim: Insulin exerts anti-apoptotic effects in both cardiomyocytes and coronary endothelial cells following ischemia / reperfusion (I / R) via the Akt-endothelial ni-tric oxide synthase survival signal pathway. Important insulin signaling may further contribute to the improvement of cardiac function after reperfusion.In this study, we tested the hypothesis that sarcoplasmic reticulum calcium-AT-Pase (SERCA2a) is involved in the insulin-induced improvement of cardiac con-tractile function following I / R. Methods: Ventricular myocytes were enzymaticallyisolated from adult SD rats . Simulated I / R was induced by perfusing cells with chemical anoxic solution for 15 min followed by reperfusion with Tyrode’s solu-tion with or without insulin for 30 min. Myocyte shortening and intracellularcalcium transients were assessed and underlying mechanisms were investigated. Results: Reperfusion with insulin (10 -7 mol / L) significantly improved the recovery of contractile function (n = 15-20 myocytes from 6-8 hearts, P <0.05 ), and increasedcalcium transients, as evidenced by the increased calcium (Ca ~ (2 +)) fluorescenceratio, shortened time to peak Ca ~ (2+) and time to 50% diastolic Ca ~ (2 +), compared withthose in cells reperfused with vehicle (P <0.05). In addition, Akt phosphorylation and SERCA2a activity were both increased in insulin-treated I / R cardiomyocytes, which were markedly inhibited by pretreatment of cells with a specific Akt inhibitor. More over, inhibition of Akt activity abolished insulin- induced positive contrac-tile and calcium transients responses in I / R cardiomyocytes. Conlusion: Thesedata demonstrated for the first time that insulin improves the recovery of contrac-tile function in simulated I / R cardiomyocytes in an Akt-dependent and SERCA2a-mediated fashion.