| First Author | Zhu H | Year | 2011 |
| Journal | Cell | Volume | 147 |
| Issue | 1 | Pages | 81-94 |
| PubMed ID | 21962509 | Mgi Jnum | J:177113 |
| Mgi Id | MGI:5294254 | Doi | 10.1016/j.cell.2011.08.033 |
| Citation | Zhu H, et al. (2011) The Lin28/let-7 Axis Regulates Glucose Metabolism. Cell 147(1):81-94 |
| abstractText | The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. |
