Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging

Recent 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...

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Detalhes bibliográficos
Autores: González-Navarro, Herminia, Vinué, Ángela, Sanz, María Jesús, Delgado, Mercedes, Pozo, Miguel Angel, Serrano, Manuel, Burks, Deborah J, Andres, Vicente
Formato: artículo
Fecha de publicación:2013
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7746
Acesso em linha:http://hdl.handle.net/20.500.12105/7746
Access Level:acceso abierto
Palavra-chave:ADP-Ribosylation Factors
Aging
Animals
Cyclin-Dependent Kinase Inhibitor p16
Genome-Wide Association Study
Glucose
Insulin
Mice
Mice, Inbred C57BL
Mice, Transgenic
Glucose Intolerance
Insulin Resistance
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/7746
network_acronym_str ES
network_name_str España
repository_id_str
spelling Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with agingGonzález-Navarro, HerminiaVinué, ÁngelaSanz, María JesúsDelgado, MercedesPozo, Miguel AngelSerrano, ManuelBurks, Deborah JAndres, VicenteADP-Ribosylation FactorsAgingAnimalsCyclin-Dependent Kinase Inhibitor p16Genome-Wide Association StudyGlucoseInsulinMiceMice, Inbred C57BLMice, TransgenicGlucose IntoleranceInsulin ResistanceRecent 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.WileyMinisterio de Economía y Competitividad (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Instituto de Salud Carlos IIIFundación ProCNIC20192019-06-0620132013-02-0120132013-02-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/7746reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES SAF2007-62110 Not availableES SAF2010-16044 Not availableES SAF2008-0011 Not availableES SAF2011-23777 Not availableES PI-CP10 00555ES RD06 0014ES CP10 00555open accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/77462026-06-12T12:43:37Z
dc.title.none.fl_str_mv Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
title Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
spellingShingle Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
González-Navarro, Herminia
ADP-Ribosylation Factors
Aging
Animals
Cyclin-Dependent Kinase Inhibitor p16
Genome-Wide Association Study
Glucose
Insulin
Mice
Mice, Inbred C57BL
Mice, Transgenic
Glucose Intolerance
Insulin Resistance
title_short Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
title_full Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
title_fullStr Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
title_full_unstemmed Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
title_sort Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
dc.creator.none.fl_str_mv González-Navarro, Herminia
Vinué, Ángela
Sanz, María Jesús
Delgado, Mercedes
Pozo, Miguel Angel
Serrano, Manuel
Burks, Deborah J
Andres, Vicente
author González-Navarro, Herminia
author_facet González-Navarro, Herminia
Vinué, Ángela
Sanz, María Jesús
Delgado, Mercedes
Pozo, Miguel Angel
Serrano, Manuel
Burks, Deborah J
Andres, Vicente
author_role author
author2 Vinué, Ángela
Sanz, María Jesús
Delgado, Mercedes
Pozo, Miguel Angel
Serrano, Manuel
Burks, Deborah J
Andres, Vicente
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Instituto de Salud Carlos III
Fundación ProCNIC
dc.subject.none.fl_str_mv ADP-Ribosylation Factors
Aging
Animals
Cyclin-Dependent Kinase Inhibitor p16
Genome-Wide Association Study
Glucose
Insulin
Mice
Mice, Inbred C57BL
Mice, Transgenic
Glucose Intolerance
Insulin Resistance
topic ADP-Ribosylation Factors
Aging
Animals
Cyclin-Dependent Kinase Inhibitor p16
Genome-Wide Association Study
Glucose
Insulin
Mice
Mice, Inbred C57BL
Mice, Transgenic
Glucose Intolerance
Insulin Resistance
description Recent 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.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-02-01
2013
2013-02-01
2019
2019-06-06
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/7746
url http://hdl.handle.net/20.500.12105/7746
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES SAF2007-62110 Not available
ES SAF2010-16044 Not available
ES SAF2008-0011 Not available
ES SAF2011-23777 Not available
ES PI-CP10 00555
ES RD06 0014
ES CP10 00555
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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