Abstract:
:The GPR119 receptor is expressed predominantly in pancreatic β cells and in enteroendocrine cells. It is a major target for the development of anti-diabetic drugs that through GPR119 activation may stimulate both insulin and GLP-1 release. GPR119 can be activated by oleoylethanolamide and several other endogenous lipids containing oleic acid: these include N-oleoyl-dopamine, 1-oleoyl-lysophosphatidylcholine, generated in the tissue, and 2-oleoyl glycerol generated in the gut lumen. Thus, the well-known stimulation of GLP-1 release by dietary fat is probably not only mediated by free fatty acids acting through, for example, GPR40, but is also probably mediated in large part through the luminal formation of 2-monoacylglycerol acting on the 'fat sensor' GPR119. In the pancreas GPR119 may also be stimulated by 2-monoacylglycerol generated from local turnover of pancreatic triacylglycerol. Knowledge about the endogenous physiological ligands and their mode of interaction with GPR119 will be crucial for the development of efficient second-generation modulators of this important drug target.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Hansen HS,Rosenkilde MM,Holst JJ,Schwartz TWdoi
10.1016/j.tips.2012.03.014subject
Has Abstractpub_date
2012-07-01 00:00:00pages
374-81issue
7eissn
0165-6147issn
1873-3735pii
S0165-6147(12)00054-5journal_volume
33pub_type
杂志文章,评审abstract::Steroid hormones are recognized as producing their major long-term effects on cell structure and function via intracellular receptors acting on the expression of genes. There is now increasing evidence that steroids also affect the surface of cells and alter ion permeability, as well as release of neurohormones and ne...
journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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更新日期:2012-04-01 00:00:00
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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journal_title:Trends in pharmacological sciences
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