Source:http://linkedlifedata.com/resource/pubmed/id/16423821
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2006-1-20
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pubmed:abstractText |
The insulinotrophic effects of glucagon-like peptide 1 (GLP-1) are mediated by its seven-transmembrane receptor (GLP-1R) in pancreatic beta-cells. We have transiently transfected the GLP-1R and a proopiomelanocortin (POMC) promoter-driven human preproinsulin gene vector (pIRES) into the AtT-20 pituitary corticotrophic cell line, to investigate the possibility of creating a regulated, insulin-expressing cell line. Receptor expression was confirmed by RT-PCR and functionality was demonstrated by measuring changes in cAMP levels in response to GLP-1. Rapid (5 min) stimulation of cAMP production was observed with 100 nM GLP-1, 24 h after transfection of 2 microg GLP-1R DNA. AtT-20 cells co-transfected with GLP-1R and human glycoprotein hormone alpha-subunit or rat POMC promoters revealed GLP-1-stimulated cAMP activation of transcription. Co-transfection of the pIRES vector with the GLP-1R resulted in GLP-1-stimulated activation of POMC promoter-driven preproinsulin gene transcription but insulin secretion was not detected. However, using an adenoviral expression system to infect AtT-20 cells with GLP-1R and the preproinsulin gene (including 120 bp of its own promoter) resulted in a 6.4 +/- 0.6-fold increase in cAMP and a 4.9 +/- 0.8-fold increase in insulin secretion in response to 100 nM GLP-1. These results demonstrate, for the first time, functional GLP-1R-mediated preproinsulin gene transcription and secretion in a transplantable cell line.
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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/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon-Like Peptide 1,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Pro-Opiomelanocortin,
http://linkedlifedata.com/resource/pubmed/chemical/Proinsulin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/glucagon-like peptide receptor,
http://linkedlifedata.com/resource/pubmed/chemical/preproinsulin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-0795
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
187
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
419-27
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16423821-Cell Line,
pubmed-meshheading:16423821-Cyclic AMP,
pubmed-meshheading:16423821-Genetic Vectors,
pubmed-meshheading:16423821-Glucagon-Like Peptide 1,
pubmed-meshheading:16423821-Humans,
pubmed-meshheading:16423821-Insulin,
pubmed-meshheading:16423821-Luciferases,
pubmed-meshheading:16423821-Pituitary Gland,
pubmed-meshheading:16423821-Pro-Opiomelanocortin,
pubmed-meshheading:16423821-Proinsulin,
pubmed-meshheading:16423821-Promoter Regions, Genetic,
pubmed-meshheading:16423821-Protein Precursors,
pubmed-meshheading:16423821-Receptors, Glucagon,
pubmed-meshheading:16423821-Transcription, Genetic,
pubmed-meshheading:16423821-Transfection
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pubmed:year |
2005
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pubmed:articleTitle |
Exogenous expression of glucagon-like peptide 1 receptor and human insulin in AtT-20 corticotrophs confers cAMP-mediated gene transcription and insulin secretion.
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pubmed:affiliation |
Department of Endocrinology, Barts and the Royal London School of Medicine and Dentistry, West Smithfield, London EC1A 7BE, UK. k.k.sidhu@qmul.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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