Moreover, since diabetes led to a significant upregulation of ACE and downregulation of ACE2 in the rat CC (Figure 4), our data implies that disruption in the ACE-ACE2 balance with a resulting hyperactivity of the detrimental ACE/Ang II/AT1 receptor “branch” of the RAAS together with a concomitant attenuation of ACE2/Ang-(1-7)/Mas receptor signaling pathway is associated with the development of DMIED. Here, ACE is linked to diabetes mellitus.