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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice
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Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice

机译：核受体FXR的激活可改善糖尿病小鼠的高血糖和高脂血症

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摘要

Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitu-tively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice. Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity. We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity. In view of its central roles in coordinating regulation of both glucose and lipid metabolism, we propose that FXR agonists are promising therapeutic agents for treatment of diabetes mellitus.
机译：法尼醇X受体（FXR）在维持胆汁酸和胆固醇体内稳态中起重要作用。在这里，我们证明FXR还调节葡萄糖代谢。合成激动剂GW4064对FXR的激活或腺病毒介导的基因转移对肝脏组成性活性FXR的过表达显着降低了糖尿病db / db和野生型小鼠的血糖水平。与这些数据一致，FXR空小鼠表现出葡萄糖耐量和胰岛素不敏感性。我们进一步证明db / db小鼠中FXR的激活抑制了肝糖原异基因，并通过涉及增强胰岛素敏感性的机制增加了肝糖原合成和糖原含量。鉴于其在协调葡萄糖和脂质代谢的调节中的核心作用，我们建议FXR激动剂是用于治疗糖尿病的有前途的治疗剂。

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