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dc.contributor.authorRoberts, LDen
dc.contributor.authorAshmore, Tomen
dc.contributor.authorMcNally, BDen
dc.contributor.authorMurfitt, SAen
dc.contributor.authorFernandez, BOen
dc.contributor.authorFeelisch, Men
dc.contributor.authorLindsay, Rossen
dc.contributor.authorSiervo, Men
dc.contributor.authorWilliams, EAen
dc.contributor.authorMurray, Andrewen
dc.contributor.authorGriffin, Julianen
dc.date.accessioned2017-03-10T16:40:39Z
dc.date.available2017-03-10T16:40:39Z
dc.date.issued2017-03-01en
dc.identifier.issn0012-1797
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263028
dc.description.abstractExercise is an effective intervention for the prevention and treatment of type 2 diabetes. Skeletal muscle combines multiple signals that contribute to the beneficial effects of exercise on cardiometabolic health. Inorganic nitrate increases exercise efficiency, tolerance, and performance. The transcriptional regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) coordinates the exercise-stimulated skeletal muscle fiber-type switch from glycolytic fast-twitch (type IIb) to oxidative slow-twitch (type I) and intermediate (type IIa) fibers, an effect reversed in insulin resistance and diabetes. We found that nitrate induces PGC1α expression and a switch toward type I and IIa fibers in rat muscle and myotubes in vitro. Nitrate induces the release of exercise/PGC1α-dependent myokine FNDC5/irisin and β-aminoisobutyric acid from myotubes and muscle in rats and humans. Both exercise and nitrate stimulated PGC1α-mediated γ-aminobutyric acid (GABA) secretion from muscle. Circulating GABA concentrations were increased in exercising mice and nitrate-treated rats and humans; thus, GABA may function as an exercise/PGC1α-mediated myokine-like small molecule. Moreover, nitrate increased circulating growth hormone levels in humans and rodents. Nitrate induces physiological responses that mimic exercise training and may underlie the beneficial effects of this metabolite on exercise and cardiometabolic health.
dc.description.sponsorshipLDR is supported by the Diabetes UK RD Lawrence Fellowship (16/0005382) and the MRC-HNR Elsie Widdowson Fellowship. This work was supported by the BBSRC (Bb/H013539/2; bb/I000933/I), the British Heart Foundation and the MRC (UD99999906).
dc.languageengen
dc.language.isoenen
dc.publisherAmerican Diabetes Association
dc.titleInorganic Nitrate Mimics Exercise-Stimulated Muscular Fiber-Type Switching and Myokine and γ-Aminobutyric Acid Releaseen
dc.typeArticle
prism.endingPage688
prism.issueIdentifier3en
prism.publicationDate2017en
prism.publicationNameDiabetesen
prism.startingPage674
prism.volume66en
dc.identifier.doi10.17863/CAM.8326
dcterms.dateAccepted2016-12-18en
rioxxterms.versionofrecord10.2337/db16-0843en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-03-01en
dc.contributor.orcidLindsay, Ross [0000-0001-7760-613X]
dc.contributor.orcidMurray, Andrew [0000-0002-0929-9315]
dc.contributor.orcidGriffin, Julian [0000-0003-1336-7744]
dc.identifier.eissn1939-327X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/P011705/1)
pubs.funder-project-idBBSRC (BB/H013539/2)
cam.issuedOnline2016-12-27en


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