Additionally, in animal models of diabetes and hypertension, the synthesis and secretion of prorenin and renin are greatly augmented in the principal cells of the CD (Prieto-Carrasquero et al., 2004; Kang et al., 2008; Prieto-Carrasquero et al., 2008), supporting the concept of a local activation of a tubular renin–angiotensin system. This evidence concerns the gene REN and diabetes mellitus.