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

我们发现肥胖糖尿病小鼠肾脏中的rac1和MR被激活，口服小剂量MR阻滞剂和rac1抑制剂分别可改善肾病。体外培养的肾细胞实验表明，葡萄糖-醛固酮非依赖地通过rac1激活激活MR，抑制rac1活性可减弱葡萄糖刺激引起的MR激活。这些结果表明了rac1/MR轴在肥胖糖尿病肾脏中的重要作用，并提示了在糖尿病肾病的治疗策略中抑制rac1的可能效果，尽管降压和抗糖尿病治疗取得了显著进展，但糖尿病肾病的发生和进展仍未得到足够的预防。

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.