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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2005-2-4
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pubmed:abstractText |
The protein p27(Kip1) regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). Here we show that p27(Kip1) progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2(-/-)) or the long form of the leptin receptor (Lepr(-/-) or db/db). Deletion of the gene encoding p27(Kip1) (Cdkn1b) ameliorated hyperglycemia in these animal models of type 2 diabetes mellitus by increasing islet mass and maintaining compensatory hyperinsulinemia, effects that were attributable predominantly to stimulation of pancreatic beta-cell proliferation. Thus, p27(Kip1) contributes to beta-cell failure during the development of type 2 diabetes in Irs2(-/-) and Lepr(-/-) mice and represents a potential new target for the treatment of this condition.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Leptin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Leptin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:HashimotoNaokoN,
pubmed-author:HayashiYoshitakeY,
pubmed-author:KasugaMasatoM,
pubmed-author:KidoYoshiakiY,
pubmed-author:KotaniKoK,
pubmed-author:MatsudaTomokazuT,
pubmed-author:NakamuraTakehiroT,
pubmed-author:NakayamaKeiichi IKI,
pubmed-author:SakaueHiroshiH,
pubmed-author:UchidaTohruT,
pubmed-author:WhiteMorris FMF
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
175-82
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15685168-Animals,
pubmed-meshheading:15685168-Cell Cycle Proteins,
pubmed-meshheading:15685168-Cell Nucleus,
pubmed-meshheading:15685168-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:15685168-Diabetes Mellitus, Type 2,
pubmed-meshheading:15685168-Disease Models, Animal,
pubmed-meshheading:15685168-Enzyme Inhibitors,
pubmed-meshheading:15685168-Hyperglycemia,
pubmed-meshheading:15685168-Hyperinsulinism,
pubmed-meshheading:15685168-Insulin Receptor Substrate Proteins,
pubmed-meshheading:15685168-Insulin-Like Growth Factor I,
pubmed-meshheading:15685168-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15685168-Islets of Langerhans,
pubmed-meshheading:15685168-Leptin,
pubmed-meshheading:15685168-Mice,
pubmed-meshheading:15685168-Mice, Knockout,
pubmed-meshheading:15685168-Phosphoproteins,
pubmed-meshheading:15685168-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15685168-Proto-Oncogene Proteins,
pubmed-meshheading:15685168-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15685168-Receptors, Cell Surface,
pubmed-meshheading:15685168-Receptors, Leptin,
pubmed-meshheading:15685168-Signal Transduction,
pubmed-meshheading:15685168-Tumor Suppressor Proteins
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pubmed:year |
2005
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pubmed:articleTitle |
Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice.
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pubmed:affiliation |
Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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