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dc.contributor.authorRaichur, S
dc.contributor.authorTeh, SH
dc.contributor.authorOhwaki, K
dc.contributor.authorGaur, V
dc.contributor.authorLong, YC
dc.contributor.authorHargreaves, M
dc.contributor.authorMcGee, SL
dc.contributor.authorKusunoki, J
dc.date.available2014-05-22T07:11:38Z
dc.date.issued2012-12-01
dc.identifierpii: JME-12-0095
dc.identifier.citationRaichur, S., Teh, S. H., Ohwaki, K., Gaur, V., Long, Y. C., Hargreaves, M., McGee, S. L. & Kusunoki, J. (2012). Histone deacetylase 5 regulates glucose uptake and insulin action in muscle cells. JOURNAL OF MOLECULAR ENDOCRINOLOGY, 49 (3), pp.203-211. https://doi.org/10.1530/JME-12-0095.
dc.identifier.issn0952-5041
dc.identifier.urihttp://hdl.handle.net/11343/32829
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractThe class IIa histone deacetylases (HDACs) act as transcriptional repressors by altering chromatin structure through histone deacetylation. This family of enzymes regulates muscle development and phenotype, through regulation of muscle-specific genes including myogenin and MyoD (MYOD1). More recently, class IIa HDACs have been implicated in regulation of genes involved in glucose metabolism. However, the effects of HDAC5 on glucose metabolism and insulin action have not been directly assessed. Knockdown of HDAC5 in human primary muscle cells increased glucose uptake and was associated with increased GLUT4 (SLC2A4) expression and promoter activity but was associated with reduced GLUT1 (SLC2A1) expression. There was no change in PGC-1α (PPARGC1A) expression. The effects of HDAC5 knockdown on glucose metabolism were not due to alterations in the initiation of differentiation, as knockdown of HDAC5 after the onset of differentiation also resulted in increased glucose uptake and insulin-stimulated glycogen synthesis. These data show that inhibition of HDAC5 enhances metabolism and insulin action in muscle cells. As these processes in muscle are dysregulated in metabolic disease, HDAC inhibition could be an effective therapeutic strategy to improve muscle metabolism in these diseases. Therefore, we also examined the effects of the pan HDAC inhibitor, Scriptaid, on muscle cell metabolism. In myotubes, Scriptaid increased histone 3 acetylation, GLUT4 expression, glucose uptake and both oxidative and non-oxidative metabolic flux. Together, these data suggest that HDAC5 regulates muscle glucose metabolism and insulin action and that HDAC inhibitors can be used to modulate these parameters in muscle cells.
dc.languageEnglish
dc.publisherBIOSCIENTIFICA LTD
dc.subjectCell Metabolism; Diabetes
dc.titleHistone deacetylase 5 regulates glucose uptake and insulin action in muscle cells
dc.typeJournal Article
dc.identifier.doi10.1530/JME-12-0095
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentChancellery Research
melbourne.affiliation.facultyChancellery
melbourne.source.titleJournal of Molecular Endocrinology
melbourne.source.volume49
melbourne.source.issue3
melbourne.source.pages203-211
melbourne.publicationid190136
melbourne.elementsid421991
melbourne.contributor.authorHargreaves, Ian
dc.identifier.eissn1479-6813
melbourne.accessrightsThis item is currently not available from this repository


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