Department of Zoology, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
Department of Biology, Faculty of Science, Al-Mustansiriya University, Baghdad P.O. Box 14022, Iraq.
Int J Mol Sci. 2024 Jun 25;25(13):6922. doi: 10.3390/ijms25136922.
Tauroursodeoxycholic acid (TUDCA) is approved for the treatment of liver diseases. However, the antihyperglycemic effects/mechanisms of TUDCA are still less clear. The present study aimed to evaluate the antidiabetic action of TUDCA in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) in rats. Fifteen adult Wistar albino male rats were randomly divided into three groups (n = five in each): control, diabetic (STZ), and STZ+TUDCA. The results showed that TUDCA treatment significantly reduced blood glucose, HbA1c%, and HOMA-IR as well as elevated the insulin levels in diabetic rats. TUDCA therapy increased the incretin GLP-1 concentrations, decreased serum ceramide synthase (CS), improved the serum lipid profile, and restored the glycogen content in the liver and skeletal muscles. Furthermore, serum inflammatory parameters (such as TNF-α, IL-6, IL-1ß, and PGE-2) were substantially reduced with TUDCA treatment. In the pancreas, STZ+TUDCA-treated rats underwent an obvious enhancement of enzymatic (CAT and SOD) and non-enzymatic (GSH) antioxidant defense systems and a marked decrease in markers of the lipid peroxidation rate (MDA) and nitrosative stress (NO) compared to STZ-alone. At the molecular level, TUDCA decreased the pancreatic mRNA levels of iNOS and apoptotic-related factors (p53 and caspase-3). In conclusion, TUDCA may be useful for diabetes management and could be able to counteract diabetic disorders via anti-hyperlipidemic, antioxidant, anti-inflammatory, and anti-apoptotic actions.
牛磺熊去氧胆酸（TUDCA）已被批准用于治疗肝脏疾病。然而，TUDCA 的降血糖作用/机制仍不明确。本研究旨在评估 TUDCA 在链脲佐菌素（STZ）诱导的 2 型糖尿病（T2DM）大鼠中的抗糖尿病作用。15 只成年雄性 Wistar 白化大鼠被随机分为三组（每组 n = 5）：对照组、糖尿病组（STZ）和 STZ+TUDCA 组。结果表明，TUDCA 治疗可显著降低糖尿病大鼠的血糖、HbA1c%和 HOMA-IR，同时升高胰岛素水平。TUDCA 治疗可增加肠降血糖素 GLP-1 浓度，降低血清神经酰胺合酶（CS）水平，改善血清脂质谱，恢复肝脏和骨骼肌中的糖原含量。此外，TUDCA 治疗可显著降低血清炎症参数（如 TNF-α、IL-6、IL-1β 和 PGE-2）。在胰腺中，与 STZ 单用时相比，STZ+TUDCA 治疗组的酶（CAT 和 SOD）和非酶（GSH）抗氧化防御系统明显增强，脂质过氧化率（MDA）和硝化应激（NO）标志物明显减少。在分子水平上，TUDCA 降低了胰腺中 iNOS 和凋亡相关因子（p53 和 caspase-3）的 mRNA 水平。总之，TUDCA 可能对糖尿病的管理有用，并且能够通过抗高血脂、抗氧化、抗炎和抗凋亡作用来对抗糖尿病紊乱。
