The mechanism of mineralocorticoid receptor activation through posttranslational modifications by sugar in diabetes mellitus.

我们首次表明，盐皮质激素受体（MR），这是强烈相关的高血压和心血管损伤，是一个目标的O-GlcNAc修饰，糖的翻译后修饰之一。我们的研究结果表明，高葡萄糖条件下增强O-GlcNAc修饰的MR，这是与增加MR水平和其在体外和体内的转录活性。根据我们的研究结果，即使在循环中醛固酮水平没有增加的情况下，MR也可能被病理激活，并且MR对醛固酮的敏感性在糖尿病中被上调，我们的研究结果为MR拮抗剂在分子水平上对顽固性高血压、肾病和糖尿病相关的心血管疾病的疗效提供了新的证据。

We showed for the first time that the mineralocorticoid receptor (MR), which is strongly associated with hypertension and cardiovascular damage, is a target for O-GlcNAc modification, one of posttranslational modifications by sugar. Our results indicate that high glucose conditions enhance O-GlcNAc modification of MR, which is associated with increased MR levels and its transcriptional activities in vitro and in vivo. Based on our results, MR is supposed to be pathologically activated even in the absence of increased circulating levels of aldosterone and the sensitivity of MR to aldosterone is upregulated in diabetes mellitus.Our findings provide a new evidence for the efficacy of MR antagonists on resistant hypertension, nephropathy and cardiovascular diseases associated with diabetes mellitus in molecular levels.