文章基本信息

标题：Aldosterone induces clonal β-cell failure through glucocorticoid receptor
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作者：Fang Chen ; Jia Liu ; Yanyang Wang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep13215
出版社：Springer Nature
摘要：Aldosterone excess causes insulin resistance in peripheral tissues and directly impairs the function of clonal β -cell. The aim of this study was to investigate the molecular mechanisms involved in the aldosterone-induced impairment of clonal β -cells. As expected, aldosterone induced apoptosis and β -cell dysfunction, including impairment of insulin synthesis and secretion, which were reversed by Glucocorticoid receptor (GR) antagonists or GR-specific siRNA. However, mineralocorticoid receptor (MR) antagonists or MR-specific siRNA had no effect on impairment of clonal β -cells induced by aldosterone. Besides, aldosterone significantly decreased expression and activity of MafA, while activated JNK and p38 MAPK in a GR-dependent manner. In addition, JNK inhibitors (SP600125) and/or p38 inhibitors (SB203580) could abolish the effect of aldosterone on MafA expression and activity. Importantly, overexpression of JNK1 or p38 reversed the protective effect of a GR antagonist on the decrease of MafA expression and activity. Furthermore, aldosterone inhibits MafA expression at the transcriptional and post-transcriptional level through activation of JNK and p38, respectively. Consequently, overexpression of MafA increased synthesis and secretion of insulin, and decreased apoptosis in clonal β -cells exposed to aldosterone. These findings identified aldosterone as an inducer of clonal β -cell failure that operates through the GR-MAPK-MafA signaling pathway.