过剩4
胰岛素抵抗
内科学
葡萄糖摄取
二甲双胍
内分泌学
安普克
葡萄糖转运蛋白
胰岛素
IRS1
化学
胰岛素受体
医学
生物
蛋白激酶B
蛋白激酶A
生物化学
激酶
信号转导
作者
Huier Yuan,Yaqiu Hu,Zhu Yang,Yongneng Zhang,Chaohuan Luo,Zhi Li,Tengfei Wen,Wanling Zhuang,Jinfang Zou,Liangli Hong,Xin Zhang,Ichiro Hisatome,Tetsuya Yamamoto,Juei‐Tang Cheng
标识
DOI:10.1016/j.mce.2016.12.025
摘要
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.
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