| pubmed-article:15126243 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0011860 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C1708335 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0032105 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0021641 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0015688 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0241889 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0442805 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0205463 | lld:lifeskim |
| pubmed-article:15126243 | lifeskim:mentions | umls-concept:C0205191 | lld:lifeskim |
| pubmed-article:15126243 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:15126243 | pubmed:dateCreated | 2004-8-13 | lld:pubmed |
| pubmed-article:15126243 | pubmed:abstractText | Muscle insulin resistance develops when plasma free fatty acids (FFAs) are acutely increased to supraphysiological levels (approximately 1,500-4,000 micromol/l). However, plasma FFA levels >1,000 micromol/l are rarely observed in humans under usual living conditions, and it is unknown whether insulin action may be impaired during a sustained but physiological FFA increase to levels seen in obesity and type 2 diabetes mellitus (T2DM) (approximately 600-800 micromol/l). It is also unclear whether normal glucose-tolerant subjects with a strong family history of T2DM (FH+) would respond to a low-dose lipid infusion as individuals without any family history of T2DM (CON). To examine these questions, we studied 7 FH+ and 10 CON subjects in whom we infused saline (SAL) or low-dose Liposyn (LIP) for 4 days. On day 4, a euglycemic insulin clamp with [3-3H]glucose and indirect calorimetry was performed to assess glucose turnover, combined with vastus lateralis muscle biopsies to examine insulin signaling. LIP increased plasma FFA approximately 1.5-fold, to levels seen in T2DM. Compared with CON, FH+ were markedly insulin resistant and had severely impaired insulin signaling in response to insulin stimulation. LIP in CON reduced insulin-stimulated glucose disposal (Rd) by 25%, insulin-stimulated insulin receptor tyrosine phosphorylation by 17%, phosphatidylinositol 3-kinase activity associated with insulin receptor substrate-1 by 20%, and insulin-stimulated glycogen synthase fractional velocity over baseline (44 vs. 15%; all P < 0.05). In contrast to CON, a physiological elevation in plasma FFA in FH+ led to no further deterioration in Rd or to any additional impairment of insulin signaling. In conclusion, a 4-day physiological increase in plasma FFA to levels seen in obesity and T2DM impairs insulin action/insulin signaling in CON but does not worsen insulin resistance in FH+. Whether this lack of additional deterioration in insulin signaling in FH+ is due to already well-established lipotoxicity, or to other molecular mechanisms related to insulin resistance that are nearly maximally expressed early in life, remains to be determined. | lld:pubmed |
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| pubmed-article:15126243 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15126243 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15126243 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15126243 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15126243 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:15126243 | pubmed:issn | 0193-1849 | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:CusiKennethK | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:BerriaRachele... | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:BajajMandeepM | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:MandarinoLawr... | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:BelfortRenata... | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:SuraamornkulS... | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:DeFronzoRalph... | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:FinlaysonJean... | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:KashyapSangee... | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:Pratipranawat... | lld:pubmed |
| pubmed-article:15126243 | pubmed:author | pubmed-author:BarrentineAnd... | lld:pubmed |
| pubmed-article:15126243 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15126243 | pubmed:volume | 287 | lld:pubmed |
| pubmed-article:15126243 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15126243 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15126243 | pubmed:pagination | E537-46 | lld:pubmed |
| pubmed-article:15126243 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:15126243 | pubmed:meshHeading | pubmed-meshheading:15126243... | lld:pubmed |
| pubmed-article:15126243 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15126243 | pubmed:articleTitle | Discordant effects of a chronic physiological increase in plasma FFA on insulin signaling in healthy subjects with or without a family history of type 2 diabetes. | lld:pubmed |
| pubmed-article:15126243 | pubmed:affiliation | Diabetes Division, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. | lld:pubmed |
| pubmed-article:15126243 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15126243 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:15126243 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:15126243 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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