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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2004-7-8
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pubmed:abstractText |
Inducible nitric oxide synthetase plays an essential role in insulin resistance induced by a high-fat diet. The reaction of nitric oxide with superoxide leads to the formation of peroxynitrite (ONOO-), which can modify several proteins. In this study, we investigated whether peroxynitrite impairs insulin-signalling pathway. Our experiments showed that 3-(4-morpholinyl)sydnonimine hydrochloride (SIN-1), a constitutive producer of peroxynitrite, dose-dependently inhibited insulin-stimulated glucose uptake. While SIN-1 did not affect the insulin receptor protein level and tyrosine phosphorylation, it reduced the insulin receptor substrate-1 (IRS-1) protein level, and IRS-1 associated phosphatidylinositol-3 kinase (PI-3 kinase) activity. Although SIN-1 did not induce Ser307 phosphorylation of IRS-1, tyrosine nitration of IRS-1 was detected in SIN-1-treated-Rat1 fibroblasts expressing human insulin receptors. Mass spectrometry showed that peroxynitrite induced at least four nitrated tyrosine residues in rat IRS-1, including Tyr939, which is critical for association of IRS-1 with the p85 subunit of PI-3 kinase. Our results suggest that peroxynitrite reduces the IRS-1 protein level and decreases phosphorylation of IRS-1 concurrent with nitration of its tyrosine residues.
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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/3-morpholino-sydnonimine,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Molsidomine,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrates,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxynitrous Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-291X
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pubmed:author |
pubmed-author:ChoiJong BockJB,
pubmed-author:IgarashiYasuhiroY,
pubmed-author:KashiwagiAtsunoriA,
pubmed-author:KawamoriRyuzoR,
pubmed-author:MaegawaHiroshiH,
pubmed-author:MinekiReikoR,
pubmed-author:MurayamaKimieK,
pubmed-author:NomiyamaTakashiT,
pubmed-author:OgiharaTakeshiT,
pubmed-author:TakaHikariH,
pubmed-author:TanakaYasushiY,
pubmed-author:UchidaToyoyoshiT,
pubmed-author:UchinoHiroshiH,
pubmed-author:WatadaHirotakaH
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
320
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
639-47
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15240096-3T3-L1 Cells,
pubmed-meshheading:15240096-Animals,
pubmed-meshheading:15240096-Binding Sites,
pubmed-meshheading:15240096-Dose-Response Relationship, Drug,
pubmed-meshheading:15240096-Glucose,
pubmed-meshheading:15240096-Insulin,
pubmed-meshheading:15240096-Insulin Receptor Substrate Proteins,
pubmed-meshheading:15240096-Mice,
pubmed-meshheading:15240096-Molsidomine,
pubmed-meshheading:15240096-Nitrates,
pubmed-meshheading:15240096-Peroxynitrous Acid,
pubmed-meshheading:15240096-Phosphoproteins,
pubmed-meshheading:15240096-Protein Binding,
pubmed-meshheading:15240096-Rats,
pubmed-meshheading:15240096-Tyrosine
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pubmed:year |
2004
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pubmed:articleTitle |
Reduction of insulin-stimulated glucose uptake by peroxynitrite is concurrent with tyrosine nitration of insulin receptor substrate-1.
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pubmed:affiliation |
Department of Medicine, Metabolism and Endocrinology, Juntendo University, School of Medicine, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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