{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:03:34Z","timestamp":1791227014514,"version":"4.1.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:p>\n                    The serine\/threonine protein kinase, mammalian target of rapamycin (mTOR) is regulated by insulin and nutrient availability and has been proposed to play a central role as a nutrient sensor in skeletal muscle. mTOR associates with its binding partners, raptor and rictor, to form two structurally and functionally distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) respectively. We have investigated the assembly of mTORC1\/2 and the activation of their downstream substrates (i.e. Akt, S6K1) in response to known effectors of mTOR, excess lipid availability and AMP-activated protein kinase (AMPK) activation\/exercise training in rat skeletal muscle. The\n                    <jats:italic>in vivo<\/jats:italic>\n                    formation of mTORC1 and 2 and the activation of their respective downstream substrates were increased in response to chronic (8 weeks) consumption of a high-fat diet. Diet-induced mTORC activation and skeletal muscle insulin resistance were reversed by 4 weeks of exercise training, which was associated with enhanced muscle AMPK activation. In order to determine whether AMPK activation reverses lipid-induced mTOR activation, L6 myotubes were exposed to 0.4\u200amM palmitate to activate mTORC1\/2 in the absence or presence of 5\u2032-aminoimidazole-4-carboxamide-1-\u03b2-\n                    <jats:sc>d<\/jats:sc>\n                    -ribofuranoside (AICAR). Palmitate exposure (4\u200ah) increased insulin-stimulated S6K1 Thr389 phosphorylation by 60%, indicating activation of mTORC1. AMPK activation with 1\u200amM AICAR abolished lipid-induced mTOR activation\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Our data implicates reductions in mTOR complex activation with the reversal of lipid-induced skeletal muscle insulin resistance in response to exercise training or AICAR and identifies mTOR as a potential target for the treatment of insulin resistance.\n                  <\/jats:p>","DOI":"10.1677\/joe-09-0202","type":"journal-article","created":{"date-parts":[[2009,7,2]],"date-time":"2009-07-02T22:32:14Z","timestamp":1246573934000},"page":"441-451","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":55,"title":["Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5\u2032-aminoimidazole-4-carboxamide-1-\u03b2-d-ribofuranoside"],"prefix":"10.1530","volume":"202","author":[{"given":"Donato A","family":"Rivas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben B","family":"Yaspelkis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Hawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J","family":"Lessard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/202\/3\/441.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/202\/3\/441.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:50Z","timestamp":1784555690000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/202\/3\/441-451\/21831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7,2]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1677\/joe-09-0202","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1162631.624198","asserted-by":"object"}]},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7,2]]}}}