Inhibition of beta1-adrenergic receptor-CaMKII activation by Insulin treatment improves prolonged post-ischemic cardiac remodeling and function

Objectives Chronic β1-adrenergic receptor (β1-AR)-calcium/calmodulin-dependent protein kinase II (CaMKII) activation leads to Ca2+ handling disturbances and adverse cardiac remodeling. We have previously demonstrated that insulin treatment exerts anti-apoptotic and prosurvival effects on myocardial ischemia/reperfusion. This study attempted to determine whether insulin treatment influences the prolonged ischemic cardiac remodeling and function and the underlying mechanisms. Methods Myocardial infarction (MI) was induced by left coronary artery ligation in adult male rats. Sham and MI rats were randomly treated with saline, insulin (2 U/kg/d, hypo. daily), or insulin plus wortmannin (a PI3K inhibitor) for 4 wks. Results At the end of four weeks after the ischemia surgery, MI rats receiving insulin treatment showed increased cardiac ejection fraction (46.9 %±1.5 % vs 37.4%±2.4 %, p