Metformin ameliorates high uric acid-induced insulin resistance in skeletal muscle cells.
Metformin ameliorates high uric acid-induced insulin resistance in skeletal muscle cells.
复制标题
二甲双胍可改善骨骼肌细胞中高尿酸诱导的胰岛素抵抗。
DOI：
10.1016/j.mce.2016.12.025
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Cheng J
中科院分区：
文献类型：
--
作者：
Yuan H;Hu YQ;Zhu YZ;Zhang YG;Luo CH;Li Z;Wen TF;Zhuang WL;Zou JF;Hong LL;Zhang X;Hisatome I;Yamamoto T;Cheng J
高尿酸血症与糖代谢异常和胰岛素抵抗同时发生。骨骼肌是葡萄糖摄取、处理和储存的重要器官。二甲双胍激活腺苷单磷酸活化蛋白激酶（AMPK）调节胰岛素信号，促进葡萄糖转运蛋白4型（GLUT4）易位，从而刺激葡萄糖摄取维持能量平衡。我们之前的研究表明，高尿酸（HUA）诱导骨骼肌组织胰岛素抵抗。然而，二甲双胍改善ua诱导的肌肉细胞胰岛素抵抗的机制尚不清楚，我们的目的是确定它。在本研究中，分化的C2C12细胞暴露于UA (15 mg/dl)，然后用DCFH-DA检测活性氧（ROS），用2-NBDG检测葡萄糖摄取。western blot检测胰岛素受体底物1 （IRS1; Ser307）、akt （Ser473）和GLUT4膜的表达水平。通过添加化合物C（一种AMPK抑制剂）和LY294002（一种PI3K/AKT抑制剂）来监测二甲双胍对ua诱导的胰岛素抵抗的影响。我们的数据表明，UA可以增加ROS的产生，抑制IRS1-AKT信号传导和胰岛素刺激的葡萄糖摄取，并诱导C2C12细胞的胰岛素抵抗。二甲双胍可以通过增加细胞内葡萄糖摄取和改善ua诱导的胰岛素抵抗来逆转这一过程。
Hyperuricemia occurs together with abnormal glucose metabolism and insulin resistance. Skeletal muscle is an important organ of glucose uptake, disposal, and storage. Metformin activates adenosine monophosphate-activated protein kinase (AMPK) to regulate insulin signaling and promote the translocation of glucose transporter type 4 (GLUT4), thereby stimulating glucose uptake to maintain energy balance. Our previous study showed that high uric acid (HUA) induced insulin resistance in skeletal muscle tissue. However, the mechanism of metformin ameliorating UA-induced insulin resistance in muscle cells is unknown and we aimed to determine it. In this study, differentiated C2C12 cells were exposed to UA (15 mg/dl), then reactive oxygen species (ROS) was detected with DCFH-DA and glucose uptake with 2-NBDG. The levels of phospho-insulin receptor substrate 1 (IRS1; Ser307), phospho-AKT (Ser473) and membrane GLUT4 were examined by western blot analysis. The impact of metformin on UA-induced insulin resistance was monitored by adding Compound C, an AMPK inhibitor, and LY294002, a PI3K/AKT inhibitor. Our data indicate that UA can increase ROS production, inhibit IRS1-AKT signaling and insulin-stimulated glucose uptake, and induce insulin resistance in C2C12 cells. Metformin can reverse this process by increasing intracellular glucose uptake and ameliorating UA-induced insulin resistance.