The current study employed an in vivo mouse model of myocardial ischemia and reperfusion injury to evaluate A1R signaling and Akt phosphorylation in the hyperglycemic inhibition of ischemic preconditioning, as well as to evaluate the role of insulin in restoring the effect of ischemic preconditioning in mice with acute hyperglycemia. Here, INS is linked to myocardial ischemia.