| Muscle contraction, but not insulin, increases microvascular blood volume in the presence of free fatty acid-induced insulin resistance. | |
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MedLine Citation:
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PMID: 19675134 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Insulin and contraction each increase muscle microvascular blood volume (MBV) and glucose uptake. Inhibiting nitric oxide synthase blocks insulin's but not contraction's effects. We examined whether contraction could augment the MBV increase seen with physiologic hyperinsulinemia and whether free fatty acid (FFA)-induced insulin resistance differentially affects contraction- versus insulin-mediated increases in MBV. RESEARCH DESIGN AND METHODS: Rats were fasted overnight. Plasma FFAs were increased by intralipid/heparin infusion (3 h), insulin was increased with a euglycemic clamp (3 mU x min(-1) x kg(-1)), and hindlimb muscle contraction was electrically stimulated. Muscle MBV was measured using contrast-enhanced ultrasound. Insulin transport into muscle was measured using (125)I-insulin. BQ-123 (0.4 mg/h) was used to block the endothelin-1 (ET-1) receptor A. RESULTS: Superimposing contraction on physiologic hyperinsulinemia increased MBV within 10 min by 37 and 67% for 0.1 or 1 Hz, respectively (P < 0.01). FFA elevation alone did not affect MBV, whereas 0.1 Hz stimulation doubled MBV (P < 0.05) and increased muscle insulin uptake (P < 0.05) despite high FFA. Physiologic hyperinsulinemia during FFA elevation paradoxically decreased MBV (P < 0.05). This MBV decrease was reversed by either 0.1 Hz contraction or ET-1 receptor A antagonism, and the combination raised MBV above basal. CONCLUSIONS: Contraction recruits microvasculature beyond that seen with physiologic hyperinsulinemia by a distinct mechanism that is not blocked by FFA-induced vascular insulin resistance. The paradoxical MBV decline seen with insulin plus FFA may result from differential inhibition of insulin-stimulated nitric oxide-dependent vasodilation relative to ET-1 vasoconstriction. Our results implicate ET-1 as a potential mediator of FFA-induced vascular insulin resistance. |
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Authors:
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April C Inyard; Daniel G Chong; Alexander L Klibanov; Eugene J Barrett |
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Publication Detail:
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Type: Journal Article Date: 2009-08-12 |
Journal Detail:
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Title: Diabetes Volume: 58 ISSN: 1939-327X ISO Abbreviation: Diabetes Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-30 Completed Date: 2010-01-06 Revised Date: 2010-11-02 |
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: 2457-63 Citation Subset: AIM; IM |
Affiliation:
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University of Virginia, Charlottesville, Virginia, USA. |
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
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metabolism Animals Blood Volume / drug effects, physiology* Deoxyglucose / metabolism Electric Stimulation Fatty Acids, Nonesterified / pharmacology* Hindlimb Hyperinsulinism / physiopathology Insulin / blood, metabolism, pharmacology* Insulin Resistance / physiology* Iodine Radioisotopes Kinetics Male Microcirculation / drug effects, physiology* Muscle, Skeletal / blood supply*, drug effects, physiology* Phosphorylation Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK057878-06/DK/NIDDK NIH HHS; R01 DK057878-07/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Nonesterified; 0/Iodine Radioisotopes; 11061-68-0/Insulin; 154-17-6/Deoxyglucose; EC 2.7.11.1/AMP-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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