GPR119 as a fat sensor
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
GPR119 as a fat sensor. / Hansen, Harald S; Rosenkilde, Mette M; Holst, Jens Juul; Schwartz, Thue W.
In: Trends in Pharmacological Sciences, Vol. 33, No. 7, 07.2012, p. 374-81.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - GPR119 as a fat sensor
AU - Hansen, Harald S
AU - Rosenkilde, Mette M
AU - Holst, Jens Juul
AU - Schwartz, Thue W
N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
KW - Animals
KW - Diabetes Mellitus, Type 2
KW - Drug Design
KW - Humans
KW - Hypoglycemic Agents
KW - Mice
KW - Mice, Transgenic
KW - Molecular Targeted Therapy
KW - Oleic Acids
KW - Receptors, G-Protein-Coupled
U2 - 10.1016/j.tips.2012.03.014
DO - 10.1016/j.tips.2012.03.014
M3 - Journal article
C2 - 22560300
VL - 33
SP - 374
EP - 381
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
SN - 0165-6147
IS - 7
ER -
ID: 45841395