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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2003-8-4
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pubmed:databankReference |
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pubmed:abstractText |
Insulin is the key hormone that controls glucose homeostasis. Dysregulation of insulin function causes diabetes mellitus. Among the two major forms of diabetes, type 2 diabetes accounts for over 90% of the affected population. The incidence of type 2 diabetes is highly related to obesity. To find novel proteins potentially involved in obesity-related insulin resistance and type 2 diabetes, a functional expression screen was performed to search for genes that negatively regulate insulin signaling. Specifically, a reporter system comprised of the PEPCK promoter upstream of alkaline phosphatase was used in a hepatocyte cell-based assay to screen an expression cDNA library for genes that reverse insulin-induced repression of PEPCK transcription. The cDNA library used in this study was derived from the white adipose tissue of ob/ob mice, which are highly insulin-resistant. The mitogen-activated dual specificity protein kinase phosphatase 4 (MKP-4) was identified as a candidate gene in this screen. Here we show that MKP-4 is expressed in insulin-responsive tissues and that the expression levels are up-regulated in obese insulin-resistant rodent models. Heterologous expression of MKP-4 in preadipocytes significantly blocked insulin-induced adipogenesis, and overexpression of MKP-4 in adipocytes inhibited insulin-stimulated glucose uptake. Our data suggest that MKP-4 negatively regulates insulin signaling and, consequently, may contribute to the pathogenesis of insulin resistance.
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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/Alkaline Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Dual-Specificity Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Dusp9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/phosphoenolpyruvate carboxykinase...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30187-92
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12777378-3T3 Cells,
pubmed-meshheading:12777378-Adipocytes,
pubmed-meshheading:12777378-Alkaline Phosphatase,
pubmed-meshheading:12777378-Amino Acid Sequence,
pubmed-meshheading:12777378-Animals,
pubmed-meshheading:12777378-Blotting, Northern,
pubmed-meshheading:12777378-Cell Differentiation,
pubmed-meshheading:12777378-Cell Line,
pubmed-meshheading:12777378-DNA, Complementary,
pubmed-meshheading:12777378-Dual-Specificity Phosphatases,
pubmed-meshheading:12777378-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:12777378-Gene Library,
pubmed-meshheading:12777378-Genes, Reporter,
pubmed-meshheading:12777378-Genetic Vectors,
pubmed-meshheading:12777378-Glucose,
pubmed-meshheading:12777378-Glutathione Peroxidase,
pubmed-meshheading:12777378-Insulin,
pubmed-meshheading:12777378-Insulin Resistance,
pubmed-meshheading:12777378-Mice,
pubmed-meshheading:12777378-Molecular Sequence Data,
pubmed-meshheading:12777378-Promoter Regions, Genetic,
pubmed-meshheading:12777378-Protein Binding,
pubmed-meshheading:12777378-Protein Tyrosine Phosphatases,
pubmed-meshheading:12777378-Proteins,
pubmed-meshheading:12777378-RNA,
pubmed-meshheading:12777378-Rats,
pubmed-meshheading:12777378-Sequence Homology, Amino Acid,
pubmed-meshheading:12777378-Signal Transduction,
pubmed-meshheading:12777378-Tissue Distribution,
pubmed-meshheading:12777378-Transcription, Genetic,
pubmed-meshheading:12777378-Transfection,
pubmed-meshheading:12777378-Tumor Cells, Cultured,
pubmed-meshheading:12777378-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
Dual specificity mitogen-activated protein (MAP) kinase phosphatase-4 plays a potential role in insulin resistance.
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pubmed:affiliation |
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA. haiyan.xu@mpi.com
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pubmed:publicationType |
Journal Article
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