Document Detail


The cytoprotective effects of oleoylethanolamide in insulin-secreting cells do not require activation of GPR119.
MedLine Citation:
PMID:  22029844     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: β-cells express a range of fatty acid-responsive G protein-coupled receptors, including GPR119, which regulates insulin secretion and is seen as a potential therapeutic target in type 2 diabetes. The long-chain unsaturated fatty acid derivative oleoylethanolamide (OEA) is an endogenous agonist of GPR119 and, under certain conditions, some long-chain unsaturated fatty acids can promote β-cell cytoprotection. It is not known, however, if OEA is cytoprotective in β-cells. The present study has examined this and determined whether GPR119 is involved.
METHODS: Clonal rat insulin-secreting cell lines, BRIN-BD11 or INS-1E, were exposed to fatty acids complexed with BSA. cAMP levels, insulin release and cell viability were measured. Protein expression was studied by Western blotting and receptor expression by RT-PCR.
KEY RESULTS: GPR119 was expressed in both BRIN-BD11 and INS-1E cells and OEA was cytoprotective in these cells. However, cytoprotection was not reproduced by any of a range of selective, synthetic ligands of GPR119. The cytoprotective response to OEA was lost during exposure to inhibitors of fatty acid amide hydrolase (FAAH) suggesting that OEA per se is not the cytoprotective species but that release of free oleate is required. Similar data were obtained with anandamide, which was cytoprotective only under conditions favouring release of free arachidonate.
CONCLUSIONS AND IMPLICATIONS: Activation of GPR119 is not required to mediate the cytoprotective actions of OEA in BRIN-BD11 or INS-1E cells. Rather, OEA is internalised and subjected to hydrolysis by FAAH to release free oleate, which then mediates the cytoprotection.
Authors:
Virginia M Stone; Shalinee Dhayal; David M Smith; Carol Lenaghan; Katy J Brocklehurst; Noel G Morgan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  165     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-26     Completed Date:  2012-07-27     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2758-70     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Institute of Biomedical & Clinical Sciences, Peninsula Medical School, University of Exeter, Plymouth, Devon, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Survival / drug effects
Cyclic AMP / metabolism
Cytoprotection / drug effects*
Fatty Acids / pharmacology
Insulin / secretion
Insulin-Secreting Cells / drug effects*,  metabolism
Oleic Acids / pharmacology*
Rats
Receptors, G-Protein-Coupled / agonists,  metabolism
Serum Albumin, Bovine / pharmacology
Grant Support
ID/Acronym/Agency:
//Biotechnology and Biological Sciences Research Council
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/GPR119 protein, rat; 0/Insulin; 0/Oleic Acids; 0/Receptors, G-Protein-Coupled; 0/Serum Albumin, Bovine; 0/oleoylethanolamide; 60-92-4/Cyclic AMP
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