EPO and type 2 diabetes mellitus: A recent study by Hotta et al. (2010) [78] using the OLETF rat model of type II diabetes showed that pretreatment with either opioid agonist [79] or erythropoietin (EPO) [80], known to mediate IPC signaling through Janus kinase (Jak-2), failed to elicit cardioprotection in vivo due to insufficient phosphorylation of Jak-2 and Akt, and like others, also found an elevated level of calcineurin activity in diabetic hearts [81].