Cadena Sandoval Marti, Haeusler Rebecca A
Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, NY, USA.
Department of Medicine, Columbia University Medical Center, New York, NY, USA.
Nat Rev Endocrinol. 2025 Apr;21(4):203-213. doi: 10.1038/s41574-024-01067-8. Epub 2025 Jan 6.
Type 2 diabetes mellitus is a complex disorder associated with insulin resistance and hyperinsulinaemia that is insufficient to maintain normal glucose metabolism. Changes in insulin signalling and insulin levels are thought to directly explain many of the metabolic abnormalities that occur in diabetes mellitus, such as impaired glucose disposal. However, molecules that are directly affected by abnormal insulin signalling might subsequently go on to cause secondary metabolic effects that contribute to the pathology of type 2 diabetes mellitus. In the past several years, evidence has linked insulin resistance with the concentration, composition and distribution of bile acids. As bile acids are known to regulate glucose metabolism, lipid metabolism and energy balance, these findings suggest that bile acids are potential mediators of metabolic distress in type 2 diabetes mellitus. In this Review, we highlight advances in our understanding of the complex regulation of bile acids during insulin resistance, as well as how bile acids contribute to metabolic control.
2型糖尿病是一种与胰岛素抵抗和高胰岛素血症相关的复杂疾病,胰岛素抵抗和高胰岛素血症不足以维持正常的葡萄糖代谢。胰岛素信号和胰岛素水平的变化被认为可以直接解释糖尿病中出现的许多代谢异常,比如葡萄糖处置受损。然而,受异常胰岛素信号直接影响的分子随后可能会引发继发性代谢效应,从而导致2型糖尿病的病理变化。在过去几年中,有证据表明胰岛素抵抗与胆汁酸的浓度、组成和分布有关。由于已知胆汁酸可调节葡萄糖代谢、脂质代谢和能量平衡,这些发现表明胆汁酸是2型糖尿病代谢紊乱的潜在介质。在本综述中,我们重点介绍了我们对胰岛素抵抗期间胆汁酸复杂调节的理解进展,以及胆汁酸如何有助于代谢控制。