Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou, China.
Clinical nutrition section, The First Hospital of Lanzhou University, Lanzhou, China.
Life Sci. 2019 Jul 15;229:80-92. doi: 10.1016/j.lfs.2019.05.031. Epub 2019 May 13.
Bile acids (BAs) as a kind of endogenous and signaling molecules altered under the circumstance of T2DM, which could impact on the relevant pathways to further affect the glucose metabolism and insulin secretion and might be associated with the T2DM development and restoration. However, the potential mechanisms still need more various and multifaceted studies. Here, we explored the alterations of BAs features and their mechanisms, and discussed the potential effects of the altered BAs on the glucose metabolic disorder via the relevant signaling pathways.
The high-fat diet (HFD) feeding combining with injection of low-dose streptozotocin (STZ) was employed for inducing the T2DM rat model. Based on that, we investigated the alterations of the concentrations and compositions of BAs and their mechanisms, and explored the effects of the altered BAs on the glucose metabolic disorder via farnesoid X receptor (Fxr) and G protein-coupled bile acid receptor (Tgr5)-mediated pathways.
In rats with T2DM, the BAs in rats with T2DM exhibited characteristic alterations, especially the increased ratio of 12α-OH to non-12α-OH BAs in serum, which could be ascribed to the up-regulated Cyp8b1 mRNA expression ratio in the liver. Moreover, Additionally, the altered BAs had negative effects on glucose metabolic disorder via inhibiting the Trg5/Fxr-mediated pathways in colon, liver and pancreas in rats with T2DM.
BAs in rats with T2DM exhibited the characteristic alterations, which could provide a cue for searching biomarkers of the T2DM diagnosis, and the altered BAs might aggravate the glucose metabolic disorder.
胆汁酸（BAs）作为一种内源性信号分子，在 T2DM 情况下发生改变，可影响相关通路，进一步影响葡萄糖代谢和胰岛素分泌，并可能与 T2DM 的发生和恢复有关。然而，其潜在机制仍需要更多的、多方面的研究。在这里，我们探讨了 BAs 特征的改变及其机制，并通过相关信号通路讨论了改变的 BAs 对葡萄糖代谢紊乱的潜在影响。
采用高脂饮食（HFD）喂养联合小剂量链脲佐菌素（STZ）注射诱导 T2DM 大鼠模型。在此基础上，我们研究了 BAs 浓度和组成的改变及其机制，并通过法尼醇 X 受体（Fxr）和 G 蛋白偶联胆汁酸受体（Tgr5）介导的通路探讨了改变的 BAs 对葡萄糖代谢紊乱的影响。
在 T2DM 大鼠中，T2DM 大鼠的 BAs 表现出特征性改变，特别是血清中 12α-OH 与非 12α-OH BAs 的比例增加，这可归因于肝脏中 Cyp8b1 mRNA 表达比例的上调。此外，改变的 BAs 通过抑制 Tgr5/Fxr 介导的通路对 T2DM 大鼠的结肠、肝脏和胰腺中的葡萄糖代谢紊乱产生负面影响。
T2DM 大鼠的 BAs 表现出特征性改变，这可为寻找 T2DM 诊断的生物标志物提供线索，而改变的 BAs 可能会加重葡萄糖代谢紊乱。
