dc.contributor.author | Zhu, Hao | |
dc.contributor.author | Shyh-Chang, Ng | |
dc.contributor.author | Segrè, Ayellet V. | |
dc.contributor.author | Shinoda, Gen | |
dc.contributor.author | Shah, Samar P. | |
dc.contributor.author | Einhorn, William S. | |
dc.contributor.author | Takeuchi, Ayumu | |
dc.contributor.author | Engreitz, Jesse Michael | |
dc.contributor.author | Hagan, John P. | |
dc.contributor.author | Kharas, Michael G. | |
dc.contributor.author | Urbach, Achia | |
dc.contributor.author | Thornton, James E. | |
dc.contributor.author | Triboulet, Robinson | |
dc.contributor.author | Gregory, Richard I. | |
dc.contributor.author | Altshuler, David | |
dc.contributor.author | Daley, George Q. | |
dc.date.accessioned | 2014-12-02T19:07:42Z | |
dc.date.available | 2014-12-02T19:07:42Z | |
dc.date.issued | 2011-09 | |
dc.date.submitted | 2011-05 | |
dc.identifier.issn | 00928674 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/91991 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) | en_US |
dc.description.sponsorship | Singapore. Agency for Science, Technology and Research (NSS Scholarship) | en_US |
dc.description.sponsorship | American Cancer Society (Postdoctoral Fellowship) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (NIH NIDDK Diseases Career Development Award) | en_US |
dc.description.sponsorship | American Diabetes Association (Postdoctoral Fellowship) | en_US |
dc.description.sponsorship | National Human Genome Research Institute (U.S.) | en_US |
dc.description.sponsorship | National Institute of General Medical Sciences (U.S.) | en_US |
dc.description.sponsorship | Pew Charitable Trusts (Pew Research Scholar) | en_US |
dc.description.sponsorship | Doris Duke Charitable Foundation (Distinguished Clinical Scholar) | en_US |
dc.description.sponsorship | Burroughs Wellcome Fund (Clinical Scientist Award in Translational Research) | en_US |
dc.description.sponsorship | Leukemia & Lymphoma Society of America (Clinical Scientist Award in Translational Research) | en_US |
dc.description.sponsorship | Howard Hughes Medical Institute (Investigator) | en_US |
dc.description.sponsorship | Boston Children's Hospital (Manton Center for Orphan Disease Research, Investigator) | en_US |
dc.description.sponsorship | American Cancer Society (Graduate Training in Cancer Research Grant) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier B.V. | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.cell.2011.08.033 | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | Elsevier | en_US |
dc.title | The Lin28/let-7 Axis Regulates Glucose Metabolism | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Zhu, Hao, Ng Shyh-Chang, Ayellet V. Segrè, Gen Shinoda, Samar P. Shah, William S. Einhorn, Ayumu Takeuchi, et al. “The Lin28/let-7 Axis Regulates Glucose Metabolism.” Cell 147, no. 1 (September 2011): 81–94. © 2014 Elsevier B.V. | en_US |
dc.contributor.department | Harvard University--MIT Division of Health Sciences and Technology | en_US |
dc.contributor.mitauthor | Engreitz, Jesse Michael | en_US |
dc.relation.journal | Cell | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G.; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-5754-1719 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |