Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/16535
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dc.contributor.authorWhite, Amanda T-
dc.contributor.authorMcCurdy, Carrie E-
dc.contributor.authorPhilp, Andrew-
dc.contributor.authorHamilton, David Lee-
dc.contributor.authorJohnson, Casey D-
dc.contributor.authorSchenk, Simon-
dc.date.accessioned2016-09-10T22:59:51Z-
dc.date.issued2013-07-
dc.identifier.urihttp://hdl.handle.net/1893/16535-
dc.description.abstractAims/hypothesis: The NAD+-dependent protein deacetylase sirtuin (SIRT)1 is thought to be a key regulator of skeletal muscle metabolism. However, its precise role in the regulation of insulin sensitivity is unclear. Accordingly, we sought to determine the effect of skeletal muscle-specific overexpression of SIRT1 on skeletal muscle insulin sensitivity and whole-body energy metabolism. Methods: At 10 weeks of age, mice with muscle-specific overexpression of SIRT1 and their wild-type littermates were fed a standard diet with free access to chow or an energy-restricted (60% of standard) diet for 20 days. Energy expenditure and body composition were measured by indirect calorimetry and magnetic resonance imaging, respectively. Skeletal muscle insulin-stimulated glucose uptake was measured ex vivo in soleus and extensor digitorum longus muscles using a 2-deoxyglucose uptake technique with a physiological insulin concentration of 360 pmol/l (60 μU/ml). Results: Sirt1 mRNA and SIRT1 protein levels were increased by approximately 100- and 150-fold, respectively, in skeletal muscle of mice with SIRT1 overexpression compared with wild-type mice. Despite this large-scale overexpression of SIRT1, body composition, whole-body energy expenditure, substrate oxidation and voluntary activity were comparable between genotypes. Similarly, skeletal muscle basal and insulin-stimulated glucose uptake were unaltered with SIRT1 overexpression. Finally, while 20 days of energy restriction enhanced insulin-stimulated glucose uptake in skeletal muscles of wild-type mice, no additional effect of SIRT1 overexpression was observed. Conclusions/interpretation: These results demonstrate that upregulation of SIRT1 activity in skeletal muscle does not affect whole-body energy expenditure or enhance skeletal muscle insulin sensitivity in young mice on a standard diet with free access to chow or in young mice on energy-restricted diets.en_UK
dc.language.isoen-
dc.publisherSpringer-
dc.relationWhite AT, McCurdy CE, Philp A, Hamilton DL, Johnson CD & Schenk S (2013) Skeletal muscle-specific overexpression of SIRT1 does not enhance whole-body energy expenditure or insulin sensitivity in young mice, Diabetologia, 56 (7), pp. 1629-1637.-
dc.rightsThe publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.-
dc.subject2-Deoxyglucose uptakeen_UK
dc.subjectEnergy restrictionen_UK
dc.subjectInsulin sensitivityen_UK
dc.subjectSIRT1en_UK
dc.subjectSkeletal muscleen_UK
dc.titleSkeletal muscle-specific overexpression of SIRT1 does not enhance whole-body energy expenditure or insulin sensitivity in young miceen_UK
dc.typeJournal Articleen_UK
dc.rights.embargodate2999-12-31T00:00:00Z-
dc.rights.embargoreasonThe publisher does not allow this work to be made publicly available in this Repository therefore there is an embargo on the full text of the work.-
dc.identifier.doihttp://dx.doi.org/10.1007/s00125-013-2912-2-
dc.citation.jtitleDiabetologia-
dc.citation.issn0012-186x-
dc.citation.volume56-
dc.citation.issue7-
dc.citation.spage1629-
dc.citation.epage1637-
dc.citation.publicationstatusPublished-
dc.citation.peerreviewedRefereed-
dc.type.statusPublisher version (final published refereed version)-
dc.author.emaild.l.hamilton@stir.ac.uk-
dc.contributor.affiliationUniversity of California, San Diego-
dc.contributor.affiliationUniversity of Colorado-
dc.contributor.affiliationUniversity of Birmingham-
dc.contributor.affiliationSport-
dc.contributor.affiliationUniversity of California, San Diego-
dc.contributor.affiliationUniversity of California, San Diego-
dc.rights.embargoterms2999-12-31-
dc.rights.embargoliftdate2999-12-31-
dc.identifier.isi000319881300021-
Appears in Collections:Faculty of Health Sciences and Sport Journal Articles

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