Source:http://linkedlifedata.com/resource/pubmed/id/12475913
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2003-1-10
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| pubmed:abstractText |
Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. Here, we describe a novel pathway for the regulation of GIP receptor (GIPR) expression within clonal beta-cell lines, pancreatic islets, and in vivo. High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h. In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner. Both MK-886, an antagonist of PPARalpha, and a dominant negative form of PPARalpha transfected into INS(832/13) cells caused a significant reduction in GIPR expression in low, but not high, glucose conditions. Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas. Thus, evidence is presented that the GIPR is controlled at normoglycemia by the fatty acid load on the islet; however, when exposed to hyperglycemic conditions, the GIPR is down-regulated, which may contribute to the decreased responsiveness to GIP that is observed in type 2 diabetes.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Gastrointestinal Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/gastric inhibitory polypeptide...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1530-6860
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
17
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
91-3
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| pubmed:dateRevised |
2004-11-17
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| pubmed:meshHeading |
pubmed-meshheading:12475913-Animals,
pubmed-meshheading:12475913-Cell Line,
pubmed-meshheading:12475913-Dose-Response Relationship, Drug,
pubmed-meshheading:12475913-Down-Regulation,
pubmed-meshheading:12475913-Fatty Acids,
pubmed-meshheading:12475913-Gene Expression Regulation,
pubmed-meshheading:12475913-Glucose,
pubmed-meshheading:12475913-Islets of Langerhans,
pubmed-meshheading:12475913-Kinetics,
pubmed-meshheading:12475913-Models, Biological,
pubmed-meshheading:12475913-RNA, Messenger,
pubmed-meshheading:12475913-Rats,
pubmed-meshheading:12475913-Rats, Zucker,
pubmed-meshheading:12475913-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12475913-Receptors, Gastrointestinal Hormone,
pubmed-meshheading:12475913-Signal Transduction,
pubmed-meshheading:12475913-Transcription, Genetic,
pubmed-meshheading:12475913-Transcription Factors
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| pubmed:year |
2003
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| pubmed:articleTitle |
A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells.
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| pubmed:affiliation |
Department of Physiology, University of British Columbia, Vancouver Canada, V6T 1Z3.
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| pubmed:publicationType |
Journal Article
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