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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
45
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pubmed:dateCreated |
2002-11-4
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pubmed:abstractText |
Current evidence suggests that uncoupling protein-2 (UCP2) is a regulator of insulin secretion. It is also known that chronic exposure of pancreatic islets to free fatty acids (FFAs) blunts glucose-stimulated insulin secretion and is accompanied by elevated levels of UCP2. However, the mechanisms regulating expression of UCP2 in beta-cells are unknown. Here, we show that UCP2 mRNA and protein levels were increased after a 48-h exposure of INS-1(832/13) beta-cells to oleic acid (0.5 mm) by activation of the UCP2 promoter. Furthermore, progressive deletions of the mouse UCP2 promoter (from -7.3 kb to +12 bp) indicated that an enhancer region (-86/-44) was responsible for both basal and FFA-stimulated UCP2 gene transcription. This enhancer contains tightly clustered Sp1, sterol regulatory element (SRE), and double E-Box elements. While all three sequence motifs were required for basal activity of the UCP2 promoter, the mutations in either the SRE or the E-Box elements eliminated the response to FFAs. The SRE and sterol regulatory element binding protein-1 (SREBP1) appear to be crucial for the response of the UCP2 gene to FFAs, since overexpression of the nuclear forms of the SREBPs increased UCP2 promoter activity by 7-10-fold and restored the ability of E-Box mutants to respond to oleic acid. These data support a model in which SREBP is the major modulator of UCP2 gene transcription by FFA, while E-Box binding factors play a supportive role.
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pubmed:grant |
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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/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oleic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Uncoupling Agents,
http://linkedlifedata.com/resource/pubmed/chemical/mitochondrial uncoupling protein 2
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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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 |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
42639-44
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12205102-Animals,
pubmed-meshheading:12205102-Base Sequence,
pubmed-meshheading:12205102-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:12205102-Cell Line,
pubmed-meshheading:12205102-DNA-Binding Proteins,
pubmed-meshheading:12205102-Enhancer Elements, Genetic,
pubmed-meshheading:12205102-Gene Expression Regulation,
pubmed-meshheading:12205102-Ion Channels,
pubmed-meshheading:12205102-Islets of Langerhans,
pubmed-meshheading:12205102-Membrane Transport Proteins,
pubmed-meshheading:12205102-Mitochondrial Proteins,
pubmed-meshheading:12205102-Mutagenesis,
pubmed-meshheading:12205102-Mutagenesis, Site-Directed,
pubmed-meshheading:12205102-Oleic Acid,
pubmed-meshheading:12205102-Point Mutation,
pubmed-meshheading:12205102-Proteins,
pubmed-meshheading:12205102-Recombinant Proteins,
pubmed-meshheading:12205102-Sequence Deletion,
pubmed-meshheading:12205102-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:12205102-Transcription Factors,
pubmed-meshheading:12205102-Transfection,
pubmed-meshheading:12205102-Uncoupling Agents
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pubmed:year |
2002
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pubmed:articleTitle |
Regulation of the uncoupling protein-2 gene in INS-1 beta-cells by oleic acid.
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pubmed:affiliation |
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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