Treatment of the diabetic WT or ATKO mice with ACE inhibitor failed to prevent the diabetic nephropathy completely, while chronic infusion of mouse HR decoy peptide (HRP) (HRP inhibits prorenin binding to PRR and non-proteolytic activation) (Ichihara et al., 2004) completely prevented the increase in urinary protein excretion and the development of glomerulosclerosis (Ichihara et al., 2006b). Here, ACE is linked to glomerulosclerosis.