dc.contributor.author | Lamming, Dudley W. | |
dc.contributor.author | Ye, Lan | |
dc.contributor.author | Katajisto, Pekka | |
dc.contributor.author | Goncalves, Marcus D. | |
dc.contributor.author | Saitoh, Maki | |
dc.contributor.author | Stevens, Deanna M. | |
dc.contributor.author | Davis, James G. | |
dc.contributor.author | Salmon, Adam B. | |
dc.contributor.author | Richardson, Arlan | |
dc.contributor.author | Ahima, Rexford S. | |
dc.contributor.author | Guertin, David A. | |
dc.contributor.author | Baur, Joseph A. | |
dc.contributor.author | Sabatini, David | |
dc.date.accessioned | 2014-03-19T19:54:11Z | |
dc.date.available | 2014-03-19T19:54:11Z | |
dc.date.issued | 2012-03 | |
dc.date.submitted | 2011-10 | |
dc.identifier.issn | 0036-8075 | |
dc.identifier.issn | 1095-9203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/85837 | |
dc.description.abstract | Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin-mediated suppression of hepatic gluconeogenesis. Further, decreased mTORC1 signaling was sufficient to extend life span independently from changes in glucose homeostasis, as female mice heterozygous for both mTOR and mLST8 exhibited decreased mTORC1 activity and extended life span but had normal glucose tolerance and insulin sensitivity. Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo. | en_US |
dc.description.sponsorship | American Federation for Aging Research | en_US |
dc.description.sponsorship | University of Pennsylvania. Institute on Aging (Bingham Trust Pilot Award) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (NIH (CA129105)) | en_US |
dc.description.sponsorship | Starr Foundation | en_US |
dc.description.sponsorship | David H. Koch Institute for Integrative Cancer Research at MIT (Frontier Research Program award) | en_US |
dc.description.sponsorship | Ellison Medical Foundation | en_US |
dc.description.sponsorship | Damon Runyon Cancer Research Foundation (Fellowship) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.). (Ruth L. Kirschstein National Research Service Award (1F32AG032833-01A1)) | en_US |
dc.description.sponsorship | American Heart Association (postdoctoral fellowship (7600031)) | en_US |
dc.description.sponsorship | Academy of Finland | en_US |
dc.language.iso | en_US | |
dc.publisher | American Association for the Advancement of Science | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1126/science.1215135 | 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 | PMC | en_US |
dc.title | Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Lamming, D. W., L. Ye, P. Katajisto, M. D. Goncalves, M. Saitoh, D. M. Stevens, J. G. Davis, et al. “Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity.” Science 335, no. 6076 (March 29, 2012): 1638-1643. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Lamming, Dudley W. | en_US |
dc.contributor.mitauthor | Katajisto, Pekka | en_US |
dc.contributor.mitauthor | Saitoh, Maki | en_US |
dc.contributor.mitauthor | Stevens, Deanna M. | en_US |
dc.contributor.mitauthor | Guertin, David A. | en_US |
dc.contributor.mitauthor | Sabatini, David M. | en_US |
dc.relation.journal | Science | en_US |
dc.eprint.version | Author's final manuscript | 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 | Lamming, D. W.; Ye, L.; Katajisto, P.; Goncalves, M. D.; Saitoh, M.; Stevens, D. M.; Davis, J. G.; Salmon, A. B.; Richardson, A.; Ahima, R. S.; Guertin, D. A.; Sabatini, D. M.; Baur, J. A. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-0079-4467 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1446-7256 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |