MicroRNA­106b regulates skeletal muscle insulin sensitivity and glucose homeostasis by targeting mitofusion­2.

ABSTRACT

MicroRNA­106b (miR­106b) is reported to be closely associated with skeletal muscle insulin resistance. The present study further investigated the role of miR­106b in skeletal muscle insulin sensitivity and glucose homeostasis in vivo. Mice were randomly divided into 4 groups and infected with lentivirus expressing miR­106b (miR­106b mice), miR­106b sponge (miR­106b inhibition mice) or the corresponding empty vectors. Mitofusion­2 (Mfn2) protein expression levels and glucose transporter (Glut)­4 protein translocation were significantly reduced in the muscle of miR­106b mice, whereas they were unaffected in miR­106b inhibition mice. miR­106b mice had significantly increased blood glucose levels following 12 h of fasting and impaired glucose tolerance, whereas miR­106b inhibition mice had no significant alterations in fasting blood glucose levels and glucose tolerance. In vitro, the suppressive effect of miR­106b 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, miR­106b inhibition consistently increased Mfn2 protein levels and improved glucose uptake and Glut4 translocation. These results indicated that miR­106b targeted Mfn2 and regulated skeletal muscle insulin sensitivity and glucose tolerance. Therefore, increased miR­106b expression may be a potential mechanism underlying insulin resistance and type 2 diabetes.