Zhu Xing, Chen Zhen, Zhang Bin, Xie Siqi, Wang Mingchang
Altern Ther Health Med. 2024 Dec;30(12):480-485.
Type 2 Diabetes mellitus (T2DM) has reached an epidemic status worldwide. Targeting bile acid signaling has therapeutic potential for treating T2DM. However, the effect of bile acid on T2DM and related mechanisms remains unclear. Here, we explored the role of bile acid in T2DM and elucidated the mechanisms involved.
We established an STZ-induced rat model of T2DM and divided it into an bile acid-treated group and saline control group according to the random number table method. We incubated the bile acid-treated group with human bile acid via middle small intestine intubation and the saline control group was incubated with the same amount of normal saline. We compared the fasting body mass, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2h-PG), fasting plasma insulin (FINS), fasting plasma triglyceride (TG), cholesterol, and total bile acid levels between the two groups one week before surgery and one to four weeks after surgery. Mechanically, Western blot, IHC, and ELISA assays were employed to detect the effect of bile acid on the TGR5/GLP-1 and FXR/FGF15 pathways.
Bile acid injection could increase the FINS level and decrease the 2h-PBG level of T2DM rats. In addition, bile acid injection did not affect FBG, fasting body mass, TG, CH, and total bile acid. At the same time, bile acid injection could activate the TGR5/GLP-1 pathway but could not influence the FXR/FGF15 pathway.
Bile acids treatment promotes glucose homeostasis in the STZ-induced T2MD rat model via the following mechanism by activating the TGR5/GLP-1 signaling pathway rather than FXR/FGF15 pathway to improve glucose tolerance and thus achieve glucose homeostasis. The bile acid/TGR5/GLP-1 signaling pathway may be a crucial mechanism of controlling the blood glucose of T2DM rats, and TGR5/GLP-1 pathway may constitute novel targets for treating T2DM.
2型糖尿病（T2DM）在全球已呈流行态势。靶向胆汁酸信号传导对治疗T2DM具有治疗潜力。然而，胆汁酸对T2DM的影响及其相关机制仍不清楚。在此，我们探讨了胆汁酸在T2DM中的作用并阐明了其涉及的机制。
我们建立了链脲佐菌素诱导的T2DM大鼠模型，并根据随机数字表法将其分为胆汁酸治疗组和生理盐水对照组。我们通过中小肠插管将人胆汁酸孵育于胆汁酸治疗组，而生理盐水对照组则用等量的生理盐水孵育。我们比较了手术前一周以及手术后一至四周两组之间的空腹体重、空腹血糖（FBG）、餐后2小时血糖（2h-PG）、空腹血浆胰岛素（FINS）、空腹血浆甘油三酯（TG）、胆固醇和总胆汁酸水平。在机制方面，采用蛋白质免疫印迹法、免疫组织化学法和酶联免疫吸附测定法检测胆汁酸对TGR5/胰高血糖素样肽-1（GLP-1）和法尼酯X受体（FXR）/成纤维细胞生长因子15（FGF15）通路的影响。
注射胆汁酸可提高T2DM大鼠的FINS水平并降低其2h-PBG水平。此外，注射胆汁酸不影响FBG、空腹体重、TG、CH和总胆汁酸。同时，注射胆汁酸可激活TGR5/GLP-1通路，但不影响FXR/FGF15通路。
胆汁酸治疗通过激活TGR5/GLP-1信号通路而非FXR/FGF15通路来改善葡萄糖耐量从而实现血糖稳态，进而促进链脲佐菌素诱导的T2MD大鼠模型中的葡萄糖稳态。胆汁酸/TGR5/GLP-1信号通路可能是控制T2DM大鼠血糖的关键机制，且TGR5/GLP-1通路可能构成治疗T2DM的新靶点。
