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dc.contributor.authorGonzález-Navarro, Herminia
dc.contributor.authorVinué, Ángela
dc.contributor.authorSanz, María Jesús
dc.contributor.authorDelgado, Mercedes
dc.contributor.authorPozo, Miguel Angel 
dc.contributor.authorSerrano, Manuel
dc.contributor.authorBurks, Deborah J
dc.contributor.authorAndres, Vicente 
dc.date.accessioned2019-06-06T10:04:05Z
dc.date.available2019-06-06T10:04:05Z
dc.date.issued2013-02
dc.identifier.citationAging Cell. 2013; 12(1):102-11es_ES
dc.identifier.issn14749718es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7746
dc.description.abstractRecent genome-wide association studies have linked type-2 diabetes mellitus to a genomic region in chromosome 9p21 near the Ink4/Arf locus, which encodes tumor suppressors that are up-regulated in a variety of mammalian organs during aging. However, it is unclear whether the susceptibility to type-2 diabetes is associated with altered expression of the Ink4/Arf locus. In the present study, we investigated the role of Ink4/Arf in age-dependent alterations of insulin and glucose homeostasis using Super-Ink4/Arf mice which bear an extra copy of the entire Ink4/Arf locus. We find that, in contrast to age-matched wild-type controls, Super-Ink4/Arf mice do not develop glucose intolerance with aging. Insulin tolerance tests demonstrated increased insulin sensitivity in Super-Ink4/Arf compared with wild-type mice, which was accompanied by higher activation of the insulin receptor substrate (IRS)-PI3K-AKT pathway in liver, skeletal muscle and heart. Glucose uptake studies in Super-Ink4/Arf mice showed a tendency toward increased (18)F-fluorodeoxyglucose uptake in skeletal muscle compared with wild-type mice (P = 0.079). Furthermore, a positive correlation between glucose uptake and baseline glucose levels was observed in Super-Ink4/Arf mice (P < 0.008) but not in wild-type mice. Our studies reveal a protective role of the Ink4/Arf locus against the development of age-dependent insulin resistance and glucose intolerance.es_ES
dc.description.sponsorshipWork supported by grants from the Spanish Ministry of Economy and Competiveness (MINECO) and European Regional Development Fund (SAF2007-62110, SAF2010-16044, SAF2008-0011, SAF2011-23777), and from the Instituto de Salud Carlos III (FIS: PI-CP10/00555, RECAVA: RD06/0014/0021, and EMER07-12). H.G.-N. is an investigator from ‘Miguel Servet’ programme (CP10/00555) and A.V. from MINECO. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the MINECO and the Pro-CNIC Foundation.es_ES
dc.language.isoenges_ES
dc.publisherWileyes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshADP-Ribosylation Factors es_ES
dc.subject.meshAging es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshCyclin-Dependent Kinase Inhibitor p16 es_ES
dc.subject.meshGenome-Wide Association Study es_ES
dc.subject.meshGlucose es_ES
dc.subject.meshInsulin es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMice, Transgenic es_ES
dc.subject.meshGlucose Intolerance es_ES
dc.subject.meshInsulin Resistance es_ES
dc.titleIncreased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aginges_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID23107464es_ES
dc.format.volume12es_ES
dc.format.number1es_ES
dc.format.page102-11es_ES
dc.identifier.doi10.1111/acel.12023es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderFundación ProCNICes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1474-9726es_ES
dc.relation.publisherversionhttps://doi.org/10.1111/acel.12023es_ES
dc.identifier.journalAging celles_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2007-62110es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2010-16044es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2008-0011es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2011-23777es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI-CP10/00555es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD06/0014/0021es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CP10/00555es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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