{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T20:06:56Z","timestamp":1791058016213,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,6,7]],"date-time":"2013-06-07T00:00:00Z","timestamp":1370563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH"},{"name":"NIA","award":["AG 035860"],"award-info":[{"award-number":["AG 035860"]}]},{"name":"NIA","award":["AG 022308"],"award-info":[{"award-number":["AG 022308"]}]},{"name":"NCI","award":["CA 129105"],"award-info":[{"award-number":["CA 129105"]}]},{"name":"NIH\/NIA","award":["1K99AG041765-01A1"],"award-info":[{"award-number":["1K99AG041765-01A1"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["7600031"],"award-info":[{"award-number":["7600031"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Rapamycin, an inhibitor of the mechanistic target of rapamycin (m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>) signaling pathway, extends the life span of yeast, worms, flies, and mice. Interventions that promote longevity are often correlated with increased insulin sensitivity, and it therefore is surprising that chronic rapamycin treatment of mice, rats, and humans is associated with insulin resistance (<jats:italic>J Am Soc Nephrol<\/jats:italic>., <jats:bold>19<\/jats:bold>,<jats:bold> 2008, 1411; <\/jats:bold><jats:italic><jats:bold>Diabetes,<\/jats:bold><\/jats:italic> <jats:bold>00, 2010, 00; <\/jats:bold><jats:italic><jats:bold>Science<\/jats:bold><\/jats:italic>,<jats:bold> 335, 2012, 1638). We examined the effect of dietary rapamycin treatment on glucose homeostasis and insulin resistance in the genetically heterogeneous <jats:styled-content style=\"fixed-case\">HET<\/jats:styled-content>3 mouse strain, a strain in which dietary rapamycin robustly extends mean and maximum life span. We find that rapamycin treatment leads to glucose intolerance in both young and old <jats:styled-content style=\"fixed-case\">HET<\/jats:styled-content>3 mice, but in contrast to the previously reported effect of injected rapamycin in C57BL\/6 mice, <jats:styled-content style=\"fixed-case\">HET<\/jats:styled-content>3 mice treated with dietary rapamycin responded normally in an insulin tolerance test. To gauge the overall consequences of rapamycin treatment on average blood glucose levels, we measured <jats:styled-content style=\"fixed-case\">HBA<\/jats:styled-content>1c. Dietary rapamycin increased <jats:styled-content style=\"fixed-case\">HBA<\/jats:styled-content>1c over the first 3\u00a0weeks of treatment in young animals, but the effect was lost by 3\u00a0months, and no effect was detected in older animals. Our results demonstrate that the extended life span of <jats:styled-content style=\"fixed-case\">HET<\/jats:styled-content>3 mice on a rapamycin diet occurs in the absence of major changes in insulin sensitivity and highlight the importance of strain background and delivery method in testing effects of longevity interventions.<\/jats:bold><\/jats:p>","DOI":"10.1111\/acel.12097","type":"journal-article","created":{"date-parts":[[2013,5,4]],"date-time":"2013-05-04T16:58:53Z","timestamp":1367686733000},"page":"712-718","source":"Crossref","is-referenced-by-count":64,"title":["Young and old genetically heterogeneous <scp>HET<\/scp>3 mice on a rapamycin diet are glucose intolerant but insulin sensitive"],"prefix":"10.1111","volume":"12","author":[{"given":"Dudley W.","family":"Lamming","sequence":"first","affiliation":[{"name":"Whitehead Institute for Biomedical Research Cambridge MA 02142 USA"},{"name":"Department of Biology MIT Cambridge MA 02139 USA"},{"name":"Howard Hughes Medical Institute MIT Cambridge MA 02139 USA"},{"name":"Broad Institute of Harvard and MIT Seven Cambridge Center Cambridge MA 02142 USA"},{"name":"The David H. Koch Institute for Integrative Cancer Research at MIT Cambridge MA 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Physiology Institute for Diabetes, Obesity, and Metabolism Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clinton M.","family":"Astle","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory Bar Harbor ME 04609 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Baur","sequence":"additional","affiliation":[{"name":"Department of Physiology Institute for Diabetes, Obesity, and Metabolism Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Sabatini","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research Cambridge MA 02142 USA"},{"name":"Department of Biology MIT Cambridge MA 02139 USA"},{"name":"Howard Hughes Medical Institute MIT Cambridge MA 02139 USA"},{"name":"Broad Institute of Harvard and MIT Seven Cambridge Center Cambridge MA 02142 USA"},{"name":"The David H. Koch Institute for Integrative Cancer Research at MIT Cambridge MA 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Harrison","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory Bar Harbor ME 04609 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9728.2004.00097.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.03.008"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000559"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06322"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1730081"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glq155"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gls127"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201953"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08221"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.3.917"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1324"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007111202"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215135"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.12.2191"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90889.2008"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glq178"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.03.029"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-9261com"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1177221"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005050487"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.6.1487"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0834-3"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facel.12097","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facel.12097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.12097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.12097","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.12097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T07:08:35Z","timestamp":1693984115000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.12097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,7]]},"references-count":22,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1111\/acel.12097"],"URL":"https:\/\/doi.org\/10.1111\/acel.12097","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,7]]}}}