Of all the novel glucoregulatory molecules discovered in the past 20 years, bile acids (BAs) are notable for the fact that they were hiding in plain sight. BAs were well known for their requirement in dietary lipid absorption and biliary cholesterol secretion, due to their micelle-forming properties. However, it was not until 1999 that BAs were discovered to be endogenous ligands for the nuclear receptor FXR. Since that time, BAs have been shown to act through multiple receptors (PXR, VDR, TGR5 and S1PR2), as well as to have receptor-independent mechanisms (membrane dynamics, allosteric modulation of N-acyl phosphatidylethanolamine phospholipase D). We now also have an appreciation of the range of physiological, pathophysiological and therapeutic conditions in which endogenous BAs are altered, raising the possibility that BAs contribute to the effects of these conditions on glycaemia. In this Review, we highlight the mechanisms by which BAs regulate glucose homeostasis and the settings in which endogenous BAs are altered, and provide suggestions for future research.

中文翻译：

---

胆汁酸在葡萄糖代谢和胰岛素信号传导中的作用机制和研究需求。

在过去的20年中发现的所有新型糖调节分子中，胆汁酸（BAs）都以其隐藏在可见的事实而著称。BA由于具有胶束形成特性，因此对膳食脂质吸收和胆汁胆固醇分泌的需求而闻名。但是，直到1999年，BA才被发现是核受体FXR的内源性配体。自那时以来，BA已显示出通过多种受体（PXR，VDR，TGR5和S1PR2）起作用，并具有受体独立机制（膜动力学，N-酰基磷脂酰乙醇胺磷脂酶D的变构调节）。现在，我们还了解了内源性BA发生改变的生理，病理生理和治疗条件的范围，增加了BA促进这些疾病对血糖的影响的可能性。在本综述中，我们重点介绍了BA调节葡萄糖稳态的机制以及内源BA改变的环境，并为以后的研究提供了建议。