Akt is a critical node of acute myocardial insulin resistance and cardiac dysfunction after cardiopulmonary bypass

Abstract

AimsAcute myocardial insulin resistance is an independent risk factor for patients who undergo cardiac surgery with cardiopulmonary bypass (CPB). However, the underlying mechanism of insulin resistance during CPB has not been fully investigated. Materials and methodsTo explore the role of myocardial insulin resistance on the cardiac function and its underlying mechanism, CPB operation and pharmacological intervention were applied in mini pigs, and myocardial insulin signaling, glucose uptake, ATP production and cardiac function were examined. Key findingsOur data showed that CPB elicited not only hyperglycemia and hyperinsulinemia, but also inactivated Akt, and impaired the transposition of membrane glucose transporter-4 (GLUT-4), reduced glucose uptake and ATP production in the myocardium as well, which in turn was accompanied with cardiac dysfunction. Meanwhile, linear correlations were established among reduced myocardial glucose uptake, ATP production, and depressed cardiac systolic or diastolic function. Reactivation of Akt by SC79, an Akt agonist, partially alleviated myocardial insulin resistance and restored post CPB cardiac function via augmenting myocardial glucose uptake and ATP production. SignificanceThese findings revealed that acute myocardial insulin resistance due to inactivation of Akt played a key role in cardiac dysfunction post CPB via suppressing glucose metabolism related energy supply.