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The aim of this study was to investigate the molecular mechanisms involved in the aldosterone-induced impairment of clonal \u03b2-cells. As expected, aldosterone induced apoptosis and \u03b2-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 \u03b2-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 \u03b2-cells exposed to aldosterone. These findings identified aldosterone as an inducer of clonal \u03b2-cell failure that operates through the GR-MAPK-MafA signaling pathway.<\/jats:p>","DOI":"10.1038\/srep13215","type":"journal-article","created":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T10:37:11Z","timestamp":1439980631000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Aldosterone induces clonal \u03b2-cell failure through glucocorticoid receptor"],"prefix":"10.1038","volume":"5","author":[{"given":"Fang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,19]]},"reference":[{"key":"BFsrep13215_CR1","first-page":"9","volume":"13","author":"SA Atlas","year":"2007","unstructured":"Atlas, S. 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