| AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo. | |
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MedLine Citation:
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PMID: 15220186 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Insulin-stimulated glucose uptake is increased in white but not red muscle of insulin-resistant high-fat-fed (HF) rats after administration of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). To investigate whether a lesser AICAR effect on glucose uptake in red muscle was offset by a greater effect on fatty acid (FA) uptake, we examined acute effects of AICAR on muscle glucose and FA fluxes in HF rats. HF rats received AICAR (250 mg/kg) subcutaneously. At 30 min, a mixture of either (3)H-(R)-2-bromopalmitate/(14)C-palmitate or (3)H-2-deoxyglucose/(14)C-glucose was administered intravenously to assess muscle FA and glucose uptake. AICAR decreased plasma levels of glucose (approximately 25%), insulin (approximately 60%), and FAs (approximately 30%) at various times over the next 46 min (P < 0.05 vs. controls). In white muscle, AICAR increased both FA (2.4-fold) and glucose uptake (4.9-fold), associated with increased glycogen synthesis (6-fold). These effects were not observed in red muscle. We conclude that both glucose and FA fluxes are enhanced by AICAR more in white versus red muscle, consistent with the relative degree of activation of AMPK. Therefore, a lesser effect of AICAR to alleviate muscle insulin resistance in red versus white muscle is not explained by a relatively greater effect on FA uptake in the red muscle. |
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Authors:
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Miguel A Iglesias; Stuart M Furler; Gregory J Cooney; Edward W Kraegen; Ji-Ming Ye |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Diabetes Volume: 53 ISSN: 0012-1797 ISO Abbreviation: Diabetes Publication Date: 2004 Jul |
Date Detail:
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Created Date: 2004-06-28 Completed Date: 2004-09-16 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: United States |
Other Details:
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Languages: eng Pagination: 1649-54 Citation Subset: AIM; IM |
Affiliation:
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Garvan Institute of Medical Research, Sydney, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases Aminoimidazole Carboxamide / analogs & derivatives*, pharmacology* Animals Dietary Fats / administration & dosage Dose-Response Relationship, Drug Enzyme Activation / drug effects Fatty Acids / metabolism* Glucose / metabolism* Insulin Resistance Male Multienzyme Complexes / metabolism* Muscle, Skeletal / metabolism* Protein-Serine-Threonine Kinases / metabolism* Rats Rats, Wistar Ribonucleotides / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Fatty Acids; 0/Multienzyme Complexes; 0/Ribonucleotides; 3031-94-5/AICA ribonucleotide; 360-97-4/Aminoimidazole Carboxamide; 50-99-7/Glucose; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
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