| First Author | Fu X | Year | 2015 |
| Journal | J Clin Invest | Volume | 125 |
| Issue | 6 | Pages | 2497-509 |
| PubMed ID | 25961460 | Mgi Jnum | J:222948 |
| Mgi Id | MGI:5646071 | Doi | 10.1172/JCI75438 |
| Citation | Fu X, et al. (2015) MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids. J Clin Invest 125(6):2497-509 |
| abstractText | Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet-fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D. |
