ABSTRACT Now diabetes is growing to be a health problems globally. However, its specific pathogenesis still needs further exploration. Here we showed that miR-15b was upregulated in the palmitate-induced HepG2 cells and livers of hyperglycemic mice. At the same time, we confirmed that the insulin receptor was a direct target of miR-15b. Then we found that the manipulation of miR-15b expression level could affect the insulin signaling pathway of HepG2 cells and the inhibition of miR-15b in liver of ob/ob mice can improve insulin sensitivity of mice. Furthermore, our study demonstrated that palmitate could upregulate the expression of miR-15b by activating PPARα. Our findings established PPARα-responsive miR-15b as a critical regulator of hepatic insulin signaling, thus serving as a new potential therapeutic target for diabetes.

中文翻译：

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MiR-15b 可靶向胰岛素受体调节小鼠肝脏胰岛素信号

摘要 现在，糖尿病正日益成为全球性的健康问题。但其具体发病机制仍有待进一步探索。在这里，我们发现 miR-15b 在棕榈酸诱导的 HepG2 细胞和高血糖小鼠肝脏中上调。同时，我们证实胰岛素受体是 miR-15b 的直接靶点。然后我们发现操纵miR-15b表达水平可以影响HepG2细胞的胰岛素信号通路，抑制ob/ob小鼠肝脏中的miR-15b可以提高小鼠的胰岛素敏感性。此外，我们的研究表明，棕榈酸酯可以通过激活 PPARα 上调 miR-15b 的表达。我们的研究结果将 PPARα 反应性 miR-15b 确立为肝脏胰岛素信号传导的关键调节因子，从而成为糖尿病的新潜在治疗靶点。