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2-Oleoyl Glycerol Is a GPR119 Agonist and Signals GLP-1 Release in Humans.
MedLine Citation:
PMID:  21778222     Owner:  NLM     Status:  Publisher    
Objective: Dietary fat is thought to stimulate release of incretin hormones via activation of fatty acid receptors in the intestine. However, dietary fat (triacylglycerol) is digested to 2-monoacylglycerol and fatty acids. Activation of G protein-coupled receptor 119 (GPR119) stimulates glucagon-like peptide-1 (GLP-1) release from the intestinal L-cells. We aimed to investigate if 2-oleoyl glycerol (2OG) can activate GPR119 in vitro and stimulate GLP-1 secretion in vivo. Research Design and Methods: Agonist activity for various lipids was tested on transiently expressed human GPR119 in COS-7 cells. The effect of a jejunal bolus of 2 g 2OG on plasma levels of GLP-1 was evaluated in eight healthy human volunteers. The effect of 2OG was compared to an equimolar amount of oleic acid, a degradation product from 2OG, and the vehicle, glycerol. Digestion of 5 ml olive oil with pancreatic lipase will result in formation of approximately 2 g 2OG and 3.2 g oleic acid. Results: 2OG and other 2-monoacylglycerols increased intracellular concentrations of cAMP in GPR119-expressing COS-7 cells (2OG EC(50) = 2.5 μm). Administration of 2OG to humans significantly increased plasma GLP-1 (0-25 min) when compared to the two controls, oleic acid and vehicle. Plasma levels of glucose-dependent insulinotropic polypeptide also increased. Conclusion: 2OG and other 2-monoacylglycerols formed during fat digestion can activate GPR119 and cause incretin release from the human intestine. This mechanism is likely to contribute to the known stimulatory effect of dietary fat on incretin secretion, and it indicates that GPR119 is a fat sensor.
Katrine B Hansen; Mette M Rosenkilde; Filip K Knop; Niels Wellner; Thi A Diep; Jens F Rehfeld; Ulrik B Andersen; Jens J Holst; Harald S Hansen
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-21
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Clinical Physiology (K.B.H., U.B.A.), Glostrup Hospital, 2600 Glostrup, Denmark; Departments of Biomedical Sciences (K.B.H., J.J.H.) and Neuro Science and Pharmacology (M.M.R.), Panum Institute, 2200 Copenhagen, Denmark; Department of Internal Medicine F (F.K.K.), Gentofte Hospital, 2900 Gentofte, Denmark; and Department of Pharmacology and Pharmacotherapy (N.W., T.A.D., H.S.H.), Faculty of Pharmaceutical Sciences, and Department of Clinical Biochemistry (J.F.R.), Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
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