MicroRNA‑106b regulates skeletal muscle insulin sensitivity and glucose homeostasis by targeting mitofusion‑2.

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.