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首页> 外文期刊>The FASEB Journal >MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1
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MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1

机译：MiR-338 通过靶向 Pdx-1 控制 BPA 触发的胰岛胰岛素分泌功能障碍，从代偿到失代偿

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Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Malemice (4wk old) were treated with BPA(50 or 500mg/kg/d) for 8 wk. Whole-body glucose homeostasis, pancreatic islet morphology and function, and miR-338-mediated molecular signal transduction analyses were examined. We showed that BPA treatment ledto a disruption of glucose tolerance and a compensatory increase of pancreatic islets insulin secretion and pancreatic and duodenal homeobox 1 (Pdx1) expression in mice. Inhibition of Pdx1 reduced glucose-stimulated insulin secretion and ATP production in the islets of BPA-exposed mice. Based on primary pancreatic islets, we also confirmed that miR-338 regulated Pdx1 and thus contributed to BPA-induced insulin secretory dysfunction from compensation to decompensation. Shortterm BPA exposure downregulated miR-338 through activation of G-protein-coupled estrogen receptor 1 (Gpr30), whereas long-term BPA exposure upregulated miR-338 through suppression of glucagon-like peptide 1 receptor (Glp1r). Taken together, our results reveal a molecular mechanism, whereby BPA regulates Gpr30/Glp1r to mediate the expression of miR-338, which acts to control Pdx1-dependent insulin secretion. The Gpr30/Glp1r-miR-338-Pdx1 axis should be represented as a novel mechanismby which BPA induces insulin secretory dysfunction in pancreatic islets.-Wei, J., Ding, D., Wang, T., Liu, Q., Lin, Y. MiR-338 controls BPA-triggered pancreatic islet insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1.
机译：双酚A（BPA）会破坏葡萄糖稳态，损害胰岛功能;然而，这些影响背后的机制知之甚少。Malemice（4周龄）用BPA（50或500mg / kg / d）处理8周。检查全身葡萄糖稳态、胰岛形态和功能以及 miR-338 介导的分子信号转导分析。我们发现BPA治疗导致小鼠葡萄糖耐量的破坏和胰岛胰岛素分泌以及胰腺和十二指肠同源盒1（Pdx1）表达的代偿性增加。抑制 Pdx1 降低了 BPA 暴露小鼠胰岛中葡萄糖刺激的胰岛素分泌和 ATP 的产生。基于原代胰岛，我们还证实 miR-338 调节 Pdx1，从而导致 BPA 诱导的胰岛素分泌功能障碍从代偿到失代偿。短期 BPA 暴露通过激活 G 蛋白偶联雌激素受体 1 （Gpr30） 下调 miR-338，而长期 BPA 暴露通过抑制胰高血糖素样肽 1 受体 （Glp1r） 上调 miR-338。综上所述，我们的研究结果揭示了一种分子机制，即BPA调节Gpr30 / Glp1r以介导miR-338的表达，miR-338具有控制Pdx1依赖性胰岛素分泌的作用。Gpr30/Glp1r-miR-338-Pdx1轴应该表示为BPA诱导胰岛胰岛素分泌功能障碍的新机制。MiR-338 通过靶向 Pdx-1 控制 BPA 触发的胰岛胰岛素分泌功能障碍从代偿到失代偿。

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