MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2.
Type 2 diabetes mellitus (T2DM) is a major health issue that has reached epidemic status worldwide. Resistance to the pleiotropic effects of insulin represents a primary process in the development of the disease, but the molecular mechanisms leading to insulin resistance have not been elucidated completely. Literature data showed that MicroRNA-106b (miR-106b) is correlated closely with skeletal muscle insulin resistance and type 2 diabetes. In this study, the authors identiï¬ÂÂÂÂÂed Mfn2 as a direct target of miR-106b. Overexpression of miR-106b resulted in mitochondrial dysfunction and insulin resistance in C2C12 myotubes. MiR-106b was increased in insulin-resistant cultured C2C12 myotubes induced by TNF-a, and accompanied by increasing Mfn2 level, miR-106b loss of function improved mitochondrial function and insulin sensitivity impaired by TNF-a in C2C12 myotubes. In addition, MiR-106b targeted Mfn2 and regulated skeletal muscle mitochondrial function and insulin sensitivity. and demonstrated that miR-106b negatively regulated Mfn2 and skeletal muscle insulin sensitivity induced insulin resistance. These results suggest that miR-106b may represent a potential therapeutic target for the treatment of insulin resistance.
[Zhang Y, Yang L, Gao YF, Fan ZM, Cai XY, Liu MY, Guo XR, Gao CL, Xia ZK. MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2. Mol Cell Endocrinol. 2013 Aug 14;381(1-2):230-240]
