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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2006-11-6
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pubmed:abstractText |
Perturbation of endoplasmic reticulum (ER) homeostasis impairs insulin biosynthesis, beta cell survival, and glucose homeostasis. We show that a murine model of diabetes is associated with the development of ER stress in beta cells and that treatment with the GLP-1R agonist exendin-4 significantly reduced biochemical markers of islet ER stress in vivo. Exendin-4 attenuated translational downregulation of insulin and improved cell survival in purified rat beta cells and in INS-1 cells following induction of ER stress in vitro. GLP-1R agonists significantly potentiated the induction of ATF-4 by ER stress and accelerated recovery from ER stress-mediated translational repression in INS-1 beta cells in a PKA-dependent manner. The effects of exendin-4 on the induction of ATF-4 were mediated via enhancement of ER stress-stimulated ATF-4 translation. Moreover, exendin-4 reduced ER stress-associated beta cell death in a PKA-dependent manner. These findings demonstrate that GLP-1R signaling directly modulates the ER stress response leading to promotion of beta cell adaptation and survival.
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pubmed:commentsCorrections |
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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/ATF4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Activating Transcription Factor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/PERK kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/Venoms,
http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/exenatide,
http://linkedlifedata.com/resource/pubmed/chemical/glucagon-like peptide receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1550-4131
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
391-406
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17084712-Activating Transcription Factor 4,
pubmed-meshheading:17084712-Animals,
pubmed-meshheading:17084712-Cell Survival,
pubmed-meshheading:17084712-Cells, Cultured,
pubmed-meshheading:17084712-Endoplasmic Reticulum,
pubmed-meshheading:17084712-Female,
pubmed-meshheading:17084712-Glucose,
pubmed-meshheading:17084712-Homeostasis,
pubmed-meshheading:17084712-Hypoglycemic Agents,
pubmed-meshheading:17084712-Insulin-Secreting Cells,
pubmed-meshheading:17084712-Mice,
pubmed-meshheading:17084712-Peptides,
pubmed-meshheading:17084712-Rats,
pubmed-meshheading:17084712-Rats, Wistar,
pubmed-meshheading:17084712-Receptors, Glucagon,
pubmed-meshheading:17084712-Stress, Physiological,
pubmed-meshheading:17084712-Up-Regulation,
pubmed-meshheading:17084712-Venoms,
pubmed-meshheading:17084712-eIF-2 Kinase
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pubmed:year |
2006
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pubmed:articleTitle |
GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress.
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pubmed:affiliation |
Department of Medicine, Banting and Best Diabetes Centre, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
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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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