Linked Life Data

18854429

Source:http://linkedlifedata.com/resource/pubmed/id/18854429

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-12-30
pubmed:abstractText
Both Epac and PKA are effectors of the second messenger cAMP. Utilizing an exchange protein directly activated by cAMP (Epac) pathway-specific cAMP analog (ESCA), we previously reported that Epac signaling regulates proglucagon gene (gcg) expression in the glucagon-like peptide-1 (GLP-1)-producing intestinal endocrine L-cell lines GLUTag and STC-1. We now show that Epac-2 is also expressed in glucagon-producing pancreatic alpha-cell lines, including PKA-deficient InR1-G9 cells, and that ESCA stimulates gcg promoter and mRNA expression in the InR1-G9 cells. Using a dominant-negative Epac-2 expression plasmid (Epac-2DN), we found that Epac inhibition attenuated forskolin-stimulated gcg promoter expression in the PKA-active STC-1 cell line and blocked forskolin-stimulated gcg promoter expression in the InR1-G9 cells. Consistently, ESCA was shown to stimulate glucagon and GLP-1 production in the InR1-G9 and GLUTag cell lines, respectively. Surprisingly, ESCA treatment did not show a notable stimulation of glucagon or GLP-1 secretion from these two cell lines. This is in contrast to its ability to stimulate insulin secretion from the pancreatic INS-1 beta-cell line. Our findings suggest that Epac is selectively involved in peptide hormone secretion in pancreatic and intestinal endocrine cells and that distinct signaling cascades are involved in stimulating production vs. secretion of glucagon and GLP-1 in response to cAMP elevation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0193-1849
pubmed:author
pubmed:issnType
Print
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E174-81
pubmed:meshHeading
pubmed-meshheading:18854429-Blotting, Northern, pubmed-meshheading:18854429-Blotting, Western, pubmed-meshheading:18854429-Cell Line, pubmed-meshheading:18854429-Cyclic AMP, pubmed-meshheading:18854429-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:18854429-Enteroendocrine Cells, pubmed-meshheading:18854429-Forskolin, pubmed-meshheading:18854429-Glucagon-Like Peptide 1, pubmed-meshheading:18854429-Glucagon-Secreting Cells, pubmed-meshheading:18854429-Guanine Nucleotide Exchange Factors, pubmed-meshheading:18854429-Humans, pubmed-meshheading:18854429-Immunohistochemistry, pubmed-meshheading:18854429-Proglucagon, pubmed-meshheading:18854429-RNA, Messenger, pubmed-meshheading:18854429-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18854429-Signal Transduction, pubmed-meshheading:18854429-Transfection
pubmed:year
2009
pubmed:articleTitle
Epac is involved in cAMP-stimulated proglucagon expression and hormone production but not hormone secretion in pancreatic alpha- and intestinal L-cell lines.
pubmed:affiliation
Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, 101 College St., Toronto, Ontario M5G 1L7.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't