法尼甾体X受体
内科学
内分泌学
葡萄糖稳态
兴奋剂
核受体
碳水化合物代谢
糖原
糖原合酶
高脂血症
脂质代谢
糖尿病
医学
胰岛素
化学
受体
生物
胰岛素抵抗
生物化学
基因
转录因子
作者
Yanqiao Zhang,Florence Ying Lee,Gabriel Barrera,Hans C. Lee,Charisse Vales,Frank J. Gonzalez,Timothy M. Willson,Peter A. Edwards
标识
DOI:10.1073/pnas.0506982103
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 constitutively 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.
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