Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6858-6863. doi: 10.3892/mmr.2017.7439. Epub 2017 Sep 8.
MicroRNA‑106b (miR‑106b) is reported to be closely associated with skeletal muscle insulin resistance. The present study further investigated the role of miR‑106b in skeletal muscle insulin sensitivity and glucose homeostasis in vivo. Mice were randomly divided into 4 groups and infected with lentivirus expressing miR‑106b (miR‑106b mice), miR‑106b sponge (miR‑106b inhibition mice) or the corresponding empty vectors. Mitofusion‑2 (Mfn2) protein expression levels and glucose transporter (Glut)‑4 protein translocation were significantly reduced in the muscle of miR‑106b mice, whereas they were unaffected in miR‑106b inhibition mice. miR‑106b mice had significantly increased blood glucose levels following 12 h of fasting and impaired glucose tolerance, whereas miR‑106b inhibition mice had no significant alterations in fasting blood glucose levels and glucose tolerance. In vitro, the suppressive effect of miR‑106b on glucose uptake and Glut4 translocation was completely inhibited in C2C12 myotubes infected with Mfn2 plasmids. Following treatment of C2C12 myotubes with Mfn2 small interfering RNA, miR‑106b inhibition consistently increased Mfn2 protein levels and improved glucose uptake and Glut4 translocation. These results indicated that miR‑106b targeted Mfn2 and regulated skeletal muscle insulin sensitivity and glucose tolerance. Therefore, increased miR‑106b expression may be a potential mechanism underlying insulin resistance and type 2 diabetes.
微小 RNA-106b（miR-106b）与骨骼肌胰岛素抵抗密切相关。本研究进一步探讨了 miR-106b 在体内骨骼肌胰岛素敏感性和葡萄糖稳态中的作用。将小鼠随机分为 4 组，分别用表达 miR-106b 的慢病毒（miR-106b 组）、miR-106b 海绵（miR-106b 抑制组）或相应的空载载体感染。miR-106b 组肌肉中的线粒体融合蛋白 2（Mfn2）蛋白表达水平和葡萄糖转运蛋白（Glut）-4 蛋白转位明显降低，而 miR-106b 抑制组无明显变化。miR-106b 组小鼠禁食 12 h 后血糖水平明显升高，糖耐量受损，而 miR-106b 抑制组小鼠空腹血糖水平和糖耐量无明显变化。在体外，感染 Mfn2 质粒的 C2C12 肌管中，miR-106b 对葡萄糖摄取和 Glut4 转位的抑制作用完全被抑制。用 Mfn2 小干扰 RNA 处理 C2C12 肌管后，miR-106b 抑制始终增加 Mfn2 蛋白水平，并改善葡萄糖摄取和 Glut4 转位。这些结果表明，miR-106b 靶向 Mfn2 并调节骨骼肌胰岛素敏感性和葡萄糖耐量。因此，miR-106b 表达增加可能是胰岛素抵抗和 2 型糖尿病的潜在机制。
