Elucidation of the role of Rac1 and MR in obese diabetic nephropathy and attempt at a novel therapeutic agent

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We showed renal Rac1 and MR activation in obese diabetic mice, and oral administration of low dose MR blockade and Rac1 inhibitor respectively ameliorated nephropathy. Experiment of cultured renal cells revealed that glucose aldosterone-independently activates MR via Rac1 activation, and suppression of Rac1 activity diminished MR activation by glucose stimulation. These result showed the important role of Rac1/MR axis in obese diabetic kidney, and suggests the possible efficacy of Rac1 suppression in the treatment strategy of diabetic nephropathy, of which incidence and progression have not been sufficiently prevented despite striking progression of antihypertensive and antidiabetic therapy.