Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model.
Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model.
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二甲双胍通过抑制高脂饮食大鼠模型中的 miR-21 表达改善骨骼肌胰岛素抵抗
DOI：
10.18632/oncotarget.20442
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发表时间：
2017-11-17
期刊：
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Wang J;Gao Y;Duan L;Wei S;Liu J;Tian L;Quan J;Zhang Q;Liu J;Yang J
胰岛素抵抗（IR）在腹部肥胖、高血压、冠心病、动脉粥样硬化和糖尿病的发病机制中起着重要作用。 miR-21和TGF-β/smads与IR密切相关。然而，二甲双胍是否通过调节 miR-21 及其靶信号 TGF-β1/smads 表达来改善骨骼肌胰岛素抵抗 (IRSM) 仍不清楚。本研究建立高脂饮食大鼠IR模型和IR-骨骼肌L6细胞(L6-SMCs)模型,应用胰岛素敏感指数(ISI)和IR稳态模型评估(HOMA-IR),RT-PCR检测miR-21和TGF-β1/smads mRNA表达量,Western blotting和激光扫描检测smad3和smad7蛋白 共聚焦显微镜（LSCM），通过荧光素酶报告基因检测检测miR-21的有效靶点。在这里，我们发现二甲双胍剂量依赖性地降低miR-21表达，伴随着HOMA-IR的降低和HOMA-ISI的增加。荧光素酶报告基因检测显示smad7是miR-21的有效靶标。 miR-21过表达直接下调smad7并间接上调smad3表达。有趣的是，miR-21表达与HOMA-IR呈正相关，与HOMA-ISI呈负相关。总之，我们的结果表明二甲双胍通过抑制 miR-21 表达改善 IRSM，并且 miR-21 可能是 IR 的治疗靶点之一。
Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-β/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-β1/smads expression. In this study, high-fat diet rats with IR model and IR-skeletal muscle L6 cells (L6-SMCs) model were established, insulin sensitive index (ISI) and Homeostasis model assessment of IR (HOMA-IR) were applied, miR-21 and TGF-β1/smads mRNA expression were examined by RT-PCR, smad3 and smad7 protein were detected by western-blotting and laser scanning confocal microscopy (LSCM), the valid target of miR-21 was detected by luciferase reporter gene assay. Here, we found that metformin dose-dependently decreased miR-21 expression, accompanied by the decrease of HOMA-IR and the increase of HOMA-ISI. Luciferase report gene assay showed that smad7 was an effective target of miR-21. miR-21 overexpression directly downregulated smad7 and indirectly upregulated smad3 expression. Interestingly, miR-21 expression positively correlated with HOMA-IR and negatively correlated with HOMA-ISI. In conclusion, our results demonstrated that metformin improved IRSM by inhibiting miR-21 expression, and that miR-21 may be one of the therapeutic targets for IR.
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影响因子：
4.6
作者：
Chen X;Yan CC;Zhang X;You ZH;Deng L;Liu Y;Zhang Y;Dai Q
通讯作者：
Dai Q
影响因子：
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作者：
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通讯作者：
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影响因子：
4.1
作者：
Wang, Jin-Yang;Gao, Yan-Bin;Yang, Jin-Kui
通讯作者：
Yang, Jin-Kui
DOI：
10.1158/1940-6207.capr-11-0299
发表时间：
2012-03
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Bao B;Wang Z;Ali S;Ahmad A;Azmi AS;Sarkar SH;Banerjee S;Kong D;Li Y;Thakur S;Sarkar FH
通讯作者：
Sarkar FH
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影响因子：
4.4
作者：
Li T;Wu R;Zhang Y;Zhu D
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