Source:http://linkedlifedata.com/resource/pubmed/id/11334412
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2001-5-3
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| pubmed:abstractText |
Tumor necrosis factor (TNF)-alpha is one of the candidate mediators of insulin resistance associated with obesity, a major risk factor for the development of type 2 diabetes. The insulin resistance induced by TNF-alpha is antagonized by thiazolidinediones (TZDs), a new class of insulin-sensitizing drugs. The aim of the current study was to dissect the mechanism whereby pioglitazone, one of the TZDs, ameliorates TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes. Pioglitazone restored insulin-stimulated 2-deoxyglucose (DOG) uptake, which was reduced by TNF-alpha, with concomitant restorations in tyrosine phosphorylation and protein levels of insulin receptor (IR) and insulin receptor substrate (IRS)-1, as well as association of the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase with IRS-1 and PI 3-kinase activity. Adenovirus-mediated gene transfer of either wild-type human peroxisome proliferator-activated receptor (PPAR)-gamma2 or a mutant carrying a replacement at the consensus mitogen-activated protein kinase phosphorylation site (hPPAR-gamma2-S112A) promoted adipogenesis of 3T3-L1 fibroblasts and restored TNF-alpha-induced decrease of triglyceride in adipocytes as effectively as pioglitazone. Overexpression of the PPAR-gamma proteins in TNF-alpha-treated adipocytes restored protein levels of IR/IRS-1, but did not improve insulin-stimulated tyrosine phosphorylation of IR/IRS-1 or insulin-stimulated 2-DOG uptake. These results indicate that the ability of pioglitazone to restore insulin-stimulated tyrosine phosphorylation of IR/IRS-1, which is necessary for amelioration of TNF-alpha-induced insulin resistance, may be independent of the adipogenic activity of PPAR-gamma that regulates protein levels of IR/IRS-1.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyglucose,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone
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| pubmed:status |
MEDLINE
|
| pubmed:month |
May
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| pubmed:issn |
0012-1797
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
50
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1083-92
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:11334412-3T3 Cells,
pubmed-meshheading:11334412-Adipocytes,
pubmed-meshheading:11334412-Animals,
pubmed-meshheading:11334412-Cell Differentiation,
pubmed-meshheading:11334412-Cell Line,
pubmed-meshheading:11334412-Deoxyglucose,
pubmed-meshheading:11334412-Humans,
pubmed-meshheading:11334412-Hypoglycemic Agents,
pubmed-meshheading:11334412-Insulin,
pubmed-meshheading:11334412-Insulin Resistance,
pubmed-meshheading:11334412-Mice,
pubmed-meshheading:11334412-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11334412-Phosphorylation,
pubmed-meshheading:11334412-Phosphotyrosine,
pubmed-meshheading:11334412-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:11334412-Recombinant Proteins,
pubmed-meshheading:11334412-Thiazoles,
pubmed-meshheading:11334412-Thiazolidinediones,
pubmed-meshheading:11334412-Transcription Factors,
pubmed-meshheading:11334412-Transfection,
pubmed-meshheading:11334412-Transforming Growth Factor alpha
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| pubmed:year |
2001
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| pubmed:articleTitle |
Pioglitazone ameliorates tumor necrosis factor-alpha-induced insulin resistance by a mechanism independent of adipogenic activity of peroxisome proliferator--activated receptor-gamma.
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| pubmed:affiliation |
First Department of Medicine, Toyama Medical and Pharmaceutical University, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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