Insulin improves cardiac myocytes contractile function recovery in simulated ischemia-reperfusion:Key role of Akt  

作　　者：ZHANG Bo, ZHANG Haifeng, FAN Qian, MA Xinliang & GAO Feng Department of Physiology, The Fourth Military Medical University,Xi抋n 710032, China Correspondence should be addressed to Gao Feng (e-mail: [e-mail]) 

出　　处：《Chinese Science Bulletin》2003年第13期1364-1369,共6页

基　　金：supported by the National Natural Science Foundation of China (Grant Nos.39970302 and 39970807);the National Science Fund for Distinguished Young Scholars(Grant No.39925013).

摘　　要：The present study examined cardiac myocytecontractile and Ca2+ transient responses to insulin duringsimulated ischemia/reperfusion (I/R) and furtherinvestigated the role of protein kinase B (Akt) in the insulin-induced inotropic effect. Ventricular myocytes wereenzymatically isolated from adult Sprague-Dawley rats and perfused with Tyrode solution while electrically field-stimulated. Simulated I/R was induced by perfusing the cells with chemical anoxic solution including sodiumcyanide-sodium lactate for 15 min followed by reperfusionwith normal oxygenated Tyrode solution with or withoutinsulin. It is found that insulin only at concentration as high as 10 IU/L could increase cell shortening (16±5%, P < 0.05) in normal myocytes, whereas it concentration-dependently (0.01—10 IU/L) increased the contraction,the velocity ofshortening/releng- thening and Ca2+ transient in I/Rmyocytes. In addition, insulin treatment (1 IU/L) increasedAkt phosphorylation of I/R cardiomyocytes by 2.4-foldcompared with that of the control (P < 0.01). Mostimportantly, pretreatment with LY 294002, a specificinhibitor of phosphatidylinositol 3′-kinase (PI3-kinase), significantly inhibited both Akt phosphorylation and thepositive inotropic response to insulin in the I/Rcardiomyocytes. These results suggest that insulin exertsdirect positive inotropic effect by increasing Ca2+ transient of cardiomyocytes, which is enhanced in the pathologicalcondition of I/R. Akt activation plays an important role inthe insulin-induced improvement of myocyte contractile function following I/R.The present study examined cardiac myocytecontractile and Ca2+ transient responses to insulin duringsimulated ischemia/reperfusion (I/R) and furtherinvestigated the role of protein kinase B (Akt) in the insulin-induced inotropic effect. Ventricular myocytes wereenzymatically isolated from adult Sprague-Dawley rats and perfused with Tyrode solution while electrically field-stimulated. Simulated I/R was induced by perfusing the cells with chemical anoxic solution including sodiumcyanide-sodium lactate for 15 min followed by reperfusionwith normal oxygenated Tyrode solution with or withoutinsulin. It is found that insulin only at concentration as high as 10 IU/L could increase cell shortening (16±5%, P < 0.05) in normal myocytes, whereas it concentration-dependently (0.01—10 IU/L) increased the contraction,the velocity ofshortening/releng- thening and Ca2+ transient in I/Rmyocytes. In addition, insulin treatment (1 IU/L) increasedAkt phosphorylation of I/R cardiomyocytes by 2.4-foldcompared with that of the control (P < 0.01). Mostimportantly, pretreatment with LY 294002, a specificinhibitor of phosphatidylinositol 3′-kinase (PI3-kinase), significantly inhibited both Akt phosphorylation and thepositive inotropic response to insulin in the I/Rcardiomyocytes. These results suggest that insulin exertsdirect positive inotropic effect by increasing Ca2+ transient of cardiomyocytes, which is enhanced in the pathologicalcondition of I/R. Akt activation plays an important role inthe insulin-induced improvement of myocyte contractile function following I/R.

关 键 词：胰岛素 心脏肌细胞 收缩功能 局部缺血 钙离子 

分 类 号：R965[医药卫生—药理学]