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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2008-5-7
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pubmed:abstractText |
Glucagon-like peptide-1 (GLP-1) is a polypeptide hormone secreted from enteroendocrine L cells and potentiates glucose-dependent insulin secretion in pancreatic beta cells. Recently the GLP-1 receptor (GLP-1 R) has been a focus for new anti-diabetic therapy with the introduction of GLP-1 analogues and DPP-IV inhibitors, and this has stimulated additional interest in the mechanisms of GLP-1 signaling. Here we identify a mechanism for GLP-1 action, showing that the scaffold protein beta-arrestin-1 mediates the effects of GLP-1 to stimulate cAMP production and insulin secretion in beta cells. Using a coimmunoprecipitation technique, we also found a physical association between the GLP-1 R and beta-arrestin-1 in cultured INS-1 pancreatic beta cells. beta-Arrestin-1 knockdown broadly attenuated GLP-1 signaling, causing decreased ERK and CREB activation and IRS-2 expression as well as reduced cAMP levels and impaired insulin secretion. However, beta-arrestin-1 knockdown did not affect GLP-1 R surface expression and ligand-induced GLP-1 R internalization/desensitization. Taken together, these studies indicate that beta-arrestin-1 plays a role in GLP-1 signaling leading to insulin secretion, defining a previously undescribed mechanism for GLP-1 action.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-10559259,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-11056535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-11278773,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-11316746,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-11546805,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-11588219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-11598134,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-12167719,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-12509508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-12574160,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-12842910,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-12879249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-1326760,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-14693691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-15456867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-15520010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-15662003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-15699045,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-15817468,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-15845844,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-16272563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-16325578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-16517403,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-16931572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17002595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17098089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17200709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17200721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17289847,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17305471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17306374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17395766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-17664271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-3033647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-9234200,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18445652-9495343
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arrestins,
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/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/beta-arrestin,
http://linkedlifedata.com/resource/pubmed/chemical/glucagon-like peptide receptor
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6614-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18445652-Animals,
pubmed-meshheading:18445652-Arrestins,
pubmed-meshheading:18445652-Cells, Cultured,
pubmed-meshheading:18445652-Cyclic AMP,
pubmed-meshheading:18445652-Endocytosis,
pubmed-meshheading:18445652-Glucagon-Like Peptide 1,
pubmed-meshheading:18445652-Insulin,
pubmed-meshheading:18445652-Insulin Receptor Substrate Proteins,
pubmed-meshheading:18445652-Insulin-Secreting Cells,
pubmed-meshheading:18445652-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:18445652-Phosphoproteins,
pubmed-meshheading:18445652-Protein Binding,
pubmed-meshheading:18445652-Rats,
pubmed-meshheading:18445652-Receptors, Glucagon,
pubmed-meshheading:18445652-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
Beta-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic beta cells.
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pubmed:affiliation |
Department of Medicine, Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla, CA 92093, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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