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

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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.