Abstract 1545: Long-Term Aerobic Exercise Sensitizes Myocardial Contractile Response to Insulin: Role of Akt-Dependent eNOS-NO Activation
Objective: It has been demonstrated that physical activity improves insulin sensitivity in skeletal muscle and liver. The present study sought to examine whether exercise sensitizes myocardial response to insulin and, if so, to further investigate the mechanism involved.
Methods: Adult male Sprague-Dawley rats were randomly subjected to 10-week free-loading swimming exercise (3 h/d, 5 d/wk) or assigned as sedentary control. The contractile responses of cardiomyocyte and perfused heart to insulin, myocardial glucose uptake, and the signaling mechanism whereby exercise improves myocardial sensitivity to insulin were investigated.
Results: Exercise significantly improved myocardial contractile response to insulin as manifested by increased myocytes shortening/relengthing (n=36–40 myocytes from 6–8 hearts/group, P<0.01) and augmented left ventricular developed pressure (ΔLVDP: 46±8 mmHg vs. 26±9 mmHg in sedentary rat hearts, n=6, P<0.05) in isolated perfused hearts. Exercise also significantly enhanced insulin-stimulated myocardial glucose uptake (1.27±0.13 μmol/g.w.w vs. 1.03±0.19 μmol/g.w.w vs. in sedentary rat hearts, n=6, P<0.05) and markedly up-regulated the expressions of Akt and eNOS by 80% and 108%, respectively (n=4, P<0.01). Treatment of the hearts with insulin (10−7 mol/L) resulted in 3.6- and 2.2-fold increases of eNOS phosphorylation (n=4, P<0.01), and 3.0- and 1.9-fold increases of Akt phosphorylation in exercise and sedentary groups, respectively (n=4, P<0.01). In addition, exercise significantly enhanced insulin-induced myocardial NO production (132±15 nmol/g protein vs. 88±19 nmol/g protein in sedentary rat hearts, n=6, P<0.01). Moreover, pretreatment with either LY294002 (a PI3-kinase inhibitor) or L-NAME (an NOS inhibitor) almost abolished the exercise-induced sensitization of myocyte contractile response to insulin, along with significant diminishes in NO production and phosphorylations of Akt and eNOS by insulin.
Conclusion: These results demonstrate that exercise sensitizes myocardial contractile response to insulin via an Akt-activated and eNOS-NO-dependent mechanism.