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Insulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxia

2016-07Journal article Restricted access
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dc.contributor.authorSacramento, J.F.
dc.contributor.authorRibeiro, M.J.
dc.contributor.authorRodrigues, T.
dc.contributor.authorGuarino, Maria Pedro
dc.contributor.authorDiogo, L.N.
dc.contributor.authorSeiça, R.
dc.contributor.authorMonteiro, E.C.
dc.contributor.authorMatafome, P.
dc.contributor.authorConde, S.V.
dc.date.accessioned2025-06-03T09:32:04Z
dc.date.available2025-06-03T09:32:04Z
dc.date.issued2016-07
dc.description.abstractChronic intermittent hypoxia (CIH) is a feature of obstructive sleep apnea (OSA). Whereas clinical stud-ies have demonstrated the association between OSA and insulin resistance, the molecular mechanismsbehind it are still unknown. Herein we investigated the effect of mild CIH on insulin sensitivity and weevaluated the changes in insulin and HIF signaling pathways that occur in CIH-induced insulin resistance.We showed that mild CIH obtained by 5/6 hypoxic (5%O2) cycles/h, 10.5 h/day during 28 and 35 daysincreased arterial blood pressure. Insulin resistance and insulinemia increased with CIH duration, beingsignificantly different after 35 days of CIH. Thirty-five days of CIH decreased insulin receptor expressionand phosphorylation in skeletal muscle and adipose tissue, but not in the liver. Conversely, Glut2 expres-sion increased in the liver of CIH-animals. Thirty-five days of CIH up-regulated HIF-1 in the liver anddown-regulated HIF-1 and HIF-2 in skeletal muscle.We concluded that the effect of CIH on insulin sensitivity and signaling is time-dependent and isassociated with changes in HIF signaling in insulin-sensitive tissues.por
dc.description.sponsorshipWe thank José Ramalho (SICGEN, Portugal) for providing the HIF-1 antibody. This study was supported by the Portuguese Foundation for Science and Technology (FCT) grants EXPL/NEU-SCC/2183/2013, PTDC/SAU-TOX/112264/2009 and by Pest-C/SAU/UI3282/2011. JFS and MJR are supported by a PhD Grantfrom FCT, PD/BD/105890/2014 and SFR/BD/88983/2012, respectively.
dc.identifier.citationJ.F. Sacramento, M.J. Ribeiro, T. Rodrigues, M.P. Guarino, L.N. Diogo, R. Seiça, E.C. Monteiro, P. Matafome, S.V. Conde, Insulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxia, Respiratory Physiology & Neurobiology, Volume 228, 2016, Pages 30-38, ISSN 1569-9048, https://doi.org/10.1016/j.resp.2016.03.007.
dc.identifier.doi10.1016/j.resp.2016.03.007
dc.identifier.issn1569-9048
dc.identifier.urihttp://hdl.handle.net/10400.8/13071
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier BV
dc.relationModulation of carotid body activity as a therapeutic intervention in metabolic diseases.
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S1569904816300246?via%3Dihub
dc.relation.ispartofRespiratory Physiology & Neurobiology
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectChronic intermittent hypoxia
dc.subjectInsulin resistance
dc.subjectObstructive sleep apnea
dc.subjectInsulin signaling and HIF signalinga
dc.titleInsulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxiaeng
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleModulation of carotid body activity as a therapeutic intervention in metabolic diseases.
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F105890%2F2014/PT
oaire.citation.endPage38
oaire.citation.startPage30
oaire.citation.titleRespiratory Physiology & Neurobiology
oaire.citation.volume228
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameGuarino
person.givenNameMaria Pedro
person.identifier.ciencia-idF21A-BD01-2D52
person.identifier.orcid0000-0001-6079-1105
person.identifier.ridB-5594-2015
person.identifier.scopus-author-id56348477000
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
relation.isAuthorOfPublicationf163d4df-1e45-4278-affa-5994f206becf
relation.isAuthorOfPublication.latestForDiscoveryf163d4df-1e45-4278-affa-5994f206becf
relation.isProjectOfPublication8d184299-84d1-4918-9ab6-1ae18bb57139
relation.isProjectOfPublication.latestForDiscovery8d184299-84d1-4918-9ab6-1ae18bb57139

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