2026-05-17T00:20:37Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/77462024-09-27T08:56:52Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
González-Navarro, Herminia
author
Vinué, Ángela
author
Sanz, María Jesús
author
Delgado, Mercedes
author
Pozo, Miguel Angel
author
Serrano, Manuel
author
Burks, Deborah J
author
Andres, Vicente
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
2019-06-06T10:04:05Z
2019-06-06T10:04:05Z
2013-02
Aging Cell. 2013; 12(1):102-11
10.1111/acel.12023
1474-9726
14749718
Aging cell
23107464
http://hdl.handle.net/20.500.12105/7746
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.
eng
Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
journal article
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IncreasedDosageIfInk4-ArtProtects_2013.pdf
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IncreasedDosageIfInk4-ArtProtects_2013_sup-1.pdf
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IncreasedDosageIfInk4-ArtProtects_2013.pdf.txt
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IncreasedDosageIfInk4-ArtProtects_2013_sup-1.pdf.txt