PuSH - Publication Server of Helmholtz Zentrum München

Zhu, H.* ; Shyh-Chang, N.* ; Segrè, A.V.* ; Shinoda, G.* ; Shah, S.P.* ; Einhorn, W.S.* ; Takeuchi, A.* ; Engreitz, J.M.* ; Hagan, J.P.* ; Kharas, M.G.* ; Urbach, A.* ; Thornton, J.E.* ; Triboulet, R.* ; Gregory, R.I* ; DIAGRAM Consortium (Huth, C. ; Grallert, H. ; Gieger, C. ; Klopp, N. ; Meitinger, T. ; Petersen, A.-K. ; Thorand, B. ; Wichmann, H.-E. ; Illig, T.) ; MAGIC Investigators (Grallert, H. ; Gieger, C. ; Meisinger, C. ; Thorand, B. ; Wichmann, H.-E. ; Illig, T.) ; Altshuler, D.* ; Daley, G.Q.*

The Lin28/let-7 axis regulates glucose metabolism.

Cell 147, 81-94 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Let-7 microrna family; Human hepatocellular-carcinoma; Caenorhabditis-elegans; Promotes transformation; Insulin-resistance; Tansgenic mice; Messenger- RNA; Stem-cells; LIN-28; LIN28
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 147, Issue: 1, Pages: 81-94 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)