| Effect of short-term free Fatty acids elevation on mitochondrial function in skeletal muscle of healthy individuals. | |
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MedLine Citation:
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PMID: 19864449 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: Mitochondrial dysfunction has been proposed as an underlying mechanism in the pathogenesis of insulin resistance and type 2 diabetes mellitus. OBJECTIVE: To determine whether mitochondrial dysfunction plays a role in the free fatty acid (FFA)-induced impairment in insulin action in skeletal muscle of healthy subjects. DESIGN: Eleven lean normal glucose tolerant individuals received 8 h lipid and saline infusion on separate days with a euglycemic insulin clamp during the last 2 h. Vastus lateralis muscle biopsies were performed at baseline and after 6 h lipid or saline infusion. Inner mitochondrial membrane potential (Psi(m)) and mitochondrial mass were determined ex vivo by confocal microscopy. RESULTS: Compared with saline infusion, lipid infusion reduced whole-body glucose uptake by 22% (P < 0.05). Psi(m) decreased by 33% (P < 0.005) after lipid infusion and the decrement in Psi(m) correlated with change in plasma FFA after lipid infusion (r = 0.753; P < 0.005). Mitochondrial content and morphology did not change after lipid infusion. No significant changes in genes expression, citrate synthase activity, and total ATP content were observed after either lipid or saline infusion. CONCLUSIONS: Short-term physiological increase in plasma FFA concentration in lean normal glucose tolerant subjects induces insulin resistance and impairs mitochondrial membrane potential but has no significant effects on mitochondrial content, gene expression, ATP content, or citrate synthase activity. |
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Authors:
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Alberto O Chavez; Subhash Kamath; Rucha Jani; Lokendra K Sharma; Adriana Monroy; Muhammad A Abdul-Ghani; Victoria E Centonze; Padma Sathyanarayana; Dawn K Coletta; Cristopher P Jenkinson; Yidong Bai; Franco Folli; Ralph A Defronzo; Devjit Tripathy |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-10-28 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 95 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-08 Completed Date: 2010-02-01 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: 422-9 Citation Subset: AIM; IM |
Affiliation:
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Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, Texas 78229, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Adult Citrate (si)-Synthase / metabolism Fatty Acids, Nonesterified / administration & dosage, blood*, pharmacology* Female Glucose / metabolism Glucose Clamp Technique Health Humans Infusions, Intravenous Insulin / blood, metabolism Lipids / administration & dosage, pharmacology Male Membrane Potential, Mitochondrial / drug effects Mitochondria, Muscle / drug effects*, genetics, metabolism, physiology Muscle, Skeletal / drug effects*, physiology Up-Regulation / physiology |
| Grant Support | |
ID/Acronym/Agency:
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DK-24092/DK/NIDDK NIH HHS; P01AG19316/AG/NIA NIH HHS; P30 AG013319/AG/NIA NIH HHS; P30 CA54174/CA/NCI NIH HHS; R01 DK079195-03/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Nonesterified; 0/Lipids; 11061-68-0/Insulin; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; EC 2.3.3.1/Citrate (si)-Synthase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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