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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2000-11-15
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pubmed:abstractText |
To investigate the role of insulin receptor substrate (IRS)-2 in vivo, we generated IRS-2-deficient mice by gene targeting. Although homozygous IRS-2-deficient mice (IRS-2-/- mice) had a body weight similar to wild-type mice, they progressively developed type 2 diabetes at 10 weeks. IRS-2-/- mice showed insulin resistance and a defect in the insulin-stimulated signaling pathway in liver but not in skeletal muscle. Despite insulin resistance, the amount of beta-cells was reduced to 83% of that in wild-type mice, which was in marked contrast to the 85% increase in the amount of beta-cells in IRS-1-deficient mice (IRS-1-/- mice) to compensate for insulin resistance. Thus, IRS-2 plays a crucial role in the regulation of beta-cell mass. On the other hand, insulin secretion by the same number of cells in response to glucose measured ex vivo was significantly increased in IRS-2-/- mice compared with wild-type mice but was decreased in IRS-1-/- mice. These results suggest that IRS-1 and IRS-2 may play different roles in the regulation of beta-cell mass and the function of individual beta-cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0012-1797
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pubmed:author |
pubmed-author:AizawaSS,
pubmed-author:AkanumaYY,
pubmed-author:EtoKK,
pubmed-author:KadowakiTT,
pubmed-author:KimuraSS,
pubmed-author:KomedaKK,
pubmed-author:KubotaNN,
pubmed-author:LesniakMM,
pubmed-author:MikiHH,
pubmed-author:NagaiRR,
pubmed-author:NakanoRR,
pubmed-author:SatohSS,
pubmed-author:SciacchitanoSS,
pubmed-author:SekiharaHH,
pubmed-author:SuzukiRR,
pubmed-author:TaylorS ISI,
pubmed-author:TerauchiYY,
pubmed-author:TobeKK,
pubmed-author:TsubamotoYY,
pubmed-author:YamauchiTT
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pubmed:issnType |
Print
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1880-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11078455-Animals,
pubmed-meshheading:11078455-Diabetes Mellitus, Type 2,
pubmed-meshheading:11078455-Gene Targeting,
pubmed-meshheading:11078455-Hyperplasia,
pubmed-meshheading:11078455-Insulin,
pubmed-meshheading:11078455-Insulin Receptor Substrate Proteins,
pubmed-meshheading:11078455-Insulin Resistance,
pubmed-meshheading:11078455-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11078455-Islets of Langerhans,
pubmed-meshheading:11078455-Liver,
pubmed-meshheading:11078455-Mice,
pubmed-meshheading:11078455-Mice, Inbred BALB C,
pubmed-meshheading:11078455-Mice, Inbred C57BL,
pubmed-meshheading:11078455-Mice, Inbred CBA,
pubmed-meshheading:11078455-Mice, Knockout,
pubmed-meshheading:11078455-Muscle, Skeletal,
pubmed-meshheading:11078455-Phosphoproteins,
pubmed-meshheading:11078455-Signal Transduction
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pubmed:year |
2000
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pubmed:articleTitle |
Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia.
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pubmed:affiliation |
Department of Metabolic Disease, Graduate School of Medicine, University of Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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