Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Intensive Critical Care Unit, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Apr 25;52(2):185-194. doi: 10.3724/zdxbyxb-2022-0647.
To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).
The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.
Asiatic acid with the dose of 25 mg·kg·d had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells and (both <0.05). Moreover, it improved the ATP production of islets of T2DM mice (<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.
Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.
研究齐墩果酸对 2 型糖尿病（T2DM）β细胞功能的影响及其分子机制。
采用高脂饮食联合链脲佐菌素（STZ）注射法建立 T2DM 模型，观察齐墩果酸对模型小鼠血糖的调节作用；采用棕榈酸处理诱导糖尿病小鼠胰岛分离，酶联免疫吸附法（ELISA）检测葡萄糖刺激的胰岛素分泌（GSIS）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平，ATP 检测试剂盒检测三磷酸腺苷（ATP）生成量，Western blot 检测成熟β细胞标志物 Ucn3 和线粒体融合蛋白 2（Mfn2）的蛋白表达。用 Mfn2 siRNA 干扰或 TNF-α处理后，观察齐墩果酸对 GSIS 和 Ucn3 表达的调节作用。
齐墩果酸 25mg·kg·d 剂量组对 T2DM 小鼠的降糖作用最佳，改善了稳态模型评估 β 指数。齐墩果酸增加了 Mfn2 和 Ucn3 蛋白的表达，改善了糖尿病β细胞的 GSIS 功能 （均<0.05），同时提高了 T2DM 小鼠胰岛的 ATP 生成量 （<0.05）。用 siRNA 干扰 Mfn2 阻断了齐墩果酸诱导的 Ucn3 上调和 GSIS。齐墩果酸抑制了胰岛 TNF-α含量，增加了 Mfn2 和 Ucn3 蛋白表达，抑制了 TNF-α诱导的 Mfn2 和 Ucn3 蛋白表达。
齐墩果酸通过维持β细胞成熟度改善 T2DM 小鼠的β细胞胰岛素分泌功能，其机制可能与 TNF-α/Mfn2 通路有关。
