AKT1 and Hyperglycemia: Furthermore, as hyperglycemia per-se suppresses Akt phosphorylation [42], our findings of reduced cardioprotection by IPC during hyperglycemia but preserved endogenous cardioprotection in diabetic animals are in support of a diverse role of PI3/Akt signaling in exogenously induced cardioprotection by IPC and the endogenous cardioprotection observed in hearts from diabetic animals.