Although renal angiotensin II level was suppressed in the AMKO-mice in the normal condition, our histological findings of increased granular cell hyperplasia and renal prorenin in AMKO-DM mice compared with those of Wild-DM mice and the findings of renal angiotensin II suppression in the chronic adrenomedullin-infused-Dahl salt sensitive rats raise the hypothesis that adrenomedullin counteracts the pathological activation of JGA and the renal renin-angiotensin system in diabetes and hypertension. This evidence concerns the gene REN and diabetes mellitus.