Role of phosphatidylinositol 3 kinase in myocardial insulin resistance induced by canine cardiopulmonary bypass ischemia reperfusion

Abstract

Objective To investigate the expression of phosphatidylinositol 3 kinase (PI3K) in the process of myocardial insulin resistance induced by extracorporal circulation ischemia repeffusion,making clear whether myocardial cells induce the transfer of glucose transporter protein-4 (Glut-4) by way of PI3K,and further probing into the mechanism of insulin resistance post-receptor in the course of cardiopulmonary bypass (CPB) ischemia.Methods Twenty-four mongrel dogs were randomly divided into 4 groups:group Ⅰ undergoing 30-min aortic occlusion; group Ⅱ undergoing 120 min aortic occlusion; group Ⅲ undergoing 30 min aortic occlusion plus insulin-PI3K activator; group Ⅳ undergoing 30 min aortic occlusion plus wortmannin-PI3K inhibitor.Samples of cardiac tissue were simultaneously collected before CPB,and 15,45 and 75 min after cross-clamp removal.The activity of PI3K and the change of myocardial cell envelope and cytoplastic Glut-4 were detected.Results The Glut-4 membrane percentage in myocardial cells were decreased in groups 1-4 from (18.68 ±6.76)％,(19.76 ±3.41)％,(17.43 ±5.36)％ and (18.43 ±4.98)％ before CPB to (3.88±1.43)％,(1.89± 1.27)％,(4.21 ± 1.59)％ and (0.65 ± 1.32)％ at the 15th min after ischemia-reperfusion,and went up slowly to various degrees at the 75th minte after the ischemia-reperfusion (P ＜ 0.01).The membrane percentage of Glut-4 in group Ⅳ,in contrast,was continuously decreased till reaching the nadir at the 75th min (P ＜ 0.05).The membrane percentage of Glut-4 in group Ⅱ,in comparison with group Ⅰ,went down strikingly in and lasted a longer time (P ＜ 0.05).The PI3K in the cardiac myocytes was declined to various extents after the ischemia reperfusion.The expression of PI3K was reduced in group Ⅰ-Ⅳ from 21.23 ± 2.58,22.73 ± 2.45,20.19 ±37.30 and 21.76 ±2.74 before CPB to 18.53 ± 1.86,15.44±9.27,24.00 ± 1.90 and 1.06 ± 0.43 at the 75th min after ischemia-reperfusion.The expression of PI3K in group Ⅳ was reduced notably in myocardial cells compared to group Ⅰ (P ＜ 0.01),whereas that in group Ⅲ was increased (P ＜ 0.05).Conclusion After the CPB ischemia-reperfusion,PI3K,as a key signal transduction factor,stimulates the transfer of Glut-4 in myocardial cellsfrom the cytoplasma to the envelope,thus assimilating glucose,namely,Glut-4 in myocardial cells is mainly transferred by way of PI3K in the process of myocardial insulin resistance induced by ischemia reperfusion. Key words: Cardiopulmonary bypass; Dog; Myocardial insulin resistance; Glucose transporter protein-4; Phosphatidylinositol 3 kinase