Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-1-20
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
419-27
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2005
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.
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
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't