ANPEP and diabetes mellitus: Thus, effective means that can activate APN signaling pathways (such as the newly identified APN receptor agonist [40] and N-Acetylcysteine [21]) may provide additional cardioprotection on top of IPo or rescue IPo cardioprotection in combating myocardial IR injury, in particular, under conditions that IPo cardioprotection is diminished or abolished such as in hearts from subjects with diabetes or the elderly [3].