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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1996-2-5
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pubmed:abstractText |
In pancreatic beta-cells, calcium is required for insulin secretion, but can also stimulate gene transcription. High potassium-induced membrane depolarization and calcium influx have previously been shown to activate kinases that phosphorylate and thereby activate the transcription factor cAMP response element (CRE-binding protein (CREB) binding to CREs. It is unknown, however, whether hormones and neurotransmitters can activate this mechanism. Arginine vasopressin (AVP), bombesin, and acetylcholine potentiate glucose-induced insulin secretion and are known to raise cytosolic calcium levels through binding to cell surface receptors that activate phospholipase C. The effect of AVP on CRE-directed transcription was examined in the beta-cell line HIT. AVP (0.1-100 nM) stimulated gene transcription after transient transfection of a reporter gene that was placed under the transcriptional control of a CRE. This effect was inhibited by a vasopressin V1 receptor antagonist and depended on calcium influx and calcineurin phosphatase activity. By immunoblots with antiphospho-CREB antibodies and by using a Gal4-CREB fusion protein, it was shown that AVP induces the phosphorylation and activation of CREB. Like AVP, bombesin (100 nM) and the muscarinic agonist carbachol (200 microM) stimulated CRE-mediated transcription. These results show that calcium-mediating insulin secretagogues can activate CREB/CRE-directed transcription in HIT cells, offering a mechanism by which these secretagogues could produce long term effects on beta-cell function, changing the pattern of gene expression.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine Vasopressin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0013-7227
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
137
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
225-33
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:8536617-Animals,
pubmed-meshheading:8536617-Arginine Vasopressin,
pubmed-meshheading:8536617-Biological Transport,
pubmed-meshheading:8536617-Calcium,
pubmed-meshheading:8536617-Cell Line,
pubmed-meshheading:8536617-Cricetinae,
pubmed-meshheading:8536617-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:8536617-Cyclosporine,
pubmed-meshheading:8536617-Insulin,
pubmed-meshheading:8536617-Islets of Langerhans,
pubmed-meshheading:8536617-Phosphorylation,
pubmed-meshheading:8536617-Tacrolimus,
pubmed-meshheading:8536617-Transcription, Genetic
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pubmed:year |
1996
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pubmed:articleTitle |
Calcium-mobilizing insulin secretagogues stimulate transcription that is directed by the cyclic adenosine 3',5'-monophosphate/calcium response element in a pancreatic islet beta-cell line.
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pubmed:affiliation |
Department of Biochemical Pharmacology, University of Gottingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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