The aromatic amino acid sensor GPR142 controls metabolism through balanced regulation of pancreatic and gut hormones.
Amino Acids, Aromatic
/ metabolism
Animals
Blood Glucose
/ metabolism
Glucagon
/ metabolism
Glucagon-Like Peptide 1
/ metabolism
Glucagon-Like Peptide-1 Receptor
/ metabolism
Glucagon-Secreting Cells
/ metabolism
Glucose
/ metabolism
Insulin
/ metabolism
Insulin-Secreting Cells
/ metabolism
Islets of Langerhans
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Obese
Rats
Rats, Zucker
Receptor-Interacting Protein Serine-Threonine Kinase 2
/ metabolism
Receptors, G-Protein-Coupled
/ biosynthesis
Receptors, Gastrointestinal Hormone
/ metabolism
Receptors, Glucagon
/ metabolism
Tryptophan
/ metabolism
Amino acid sensing
G-protein-coupled receptor
GPR142
Glucose homeostasis
Trp
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
21
09
2018
revised:
29
10
2018
accepted:
31
10
2018
pubmed:
26
11
2018
medline:
7
1
2020
entrez:
26
11
2018
Statut:
ppublish
Résumé
GPR142, which is highly expressed in pancreatic islets, has recently been deorphanized as a receptor for aromatic amino acids; however, its physiological role and pharmacological potential is unclear. We find that GPR142 is expressed not only in β- but also in α-cells of the islets as well as in enteroendocrine cells, and we confirm that GPR142 is a highly selective sensor of essential aromatic amino acids, in particular Trp and oligopeptides with N-terminal Trp. GPR142 knock-out mice displayed a very limited metabolic phenotype but demonstrated that L-Trp induced secretion of pancreatic and gut hormones is mediated through GPR142 but that the receptor is not required for protein-induced hormone secretion. A synthetic GPR142 agonist stimulated insulin and glucagon as well as GIP, CCK, and GLP-1 secretion. In particular, GIP secretion was sensitive to oral administration of the GPR142 agonist an effect which in contrast to the other hormones was blocked by protein load. Oral administration of the GPR142 agonist increased [ GPR142 functions as a sensor of aromatic amino acids, controlling GIP but also CCK and GLP-1 as well as insulin and glucagon in the pancreas. GPR142 agonists could have novel interesting potential in modifying metabolism through a balanced action of gut hormones as well as both insulin and glucagon.
Identifiants
pubmed: 30472415
pii: S2212-8778(18)30930-X
doi: 10.1016/j.molmet.2018.10.012
pmc: PMC6323244
pii:
doi:
Substances chimiques
Amino Acids, Aromatic
0
Blood Glucose
0
GPR142 protein, mouse
0
Glucagon-Like Peptide-1 Receptor
0
Insulin
0
Receptors, G-Protein-Coupled
0
Receptors, Gastrointestinal Hormone
0
Receptors, Glucagon
0
Glucagon-Like Peptide 1
89750-14-1
Tryptophan
8DUH1N11BX
Glucagon
9007-92-5
gastric inhibitory polypeptide receptor
D6H00MV7K8
Receptor-Interacting Protein Serine-Threonine Kinase 2
EC 2.7.11.1
Ripk2 protein, mouse
EC 2.7.11.1
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
49-64Subventions
Organisme : Medical Research Council
ID : MC_UU_00014/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/3
Pays : United Kingdom
Informations de copyright
Copyright © 2018. Published by Elsevier GmbH.
Références
Mol Metab. 2018 May;11:205-211
pubmed: 29506910
ACS Med Chem Lett. 2013 Jun 17;4(8):790-4
pubmed: 24900747
Diabetes. 2012 Feb;61(2):310-20
pubmed: 22210322
Nutr Metab (Lond). 2011 Jun 28;8(1):45
pubmed: 21831334
Am J Physiol Cell Physiol. 2010 Feb;298(2):C377-85
pubmed: 19923418
Physiol Behav. 2010 Jul 14;100(5):545-8
pubmed: 20381509
Gastroenterology. 2018 Oct;155(4):1164-1176.e2
pubmed: 29935151
Eur J Clin Invest. 1992 Apr;22(4):283-91
pubmed: 1499644
Diabetologia. 2018 Feb;61(2):284-294
pubmed: 28956082
FEBS J. 2008 Sep;275(18):4620-6
pubmed: 18691347
Endocrinology. 1991 Jun;128(6):3175-82
pubmed: 1674688
Nutr Metab (Lond). 2008 Aug 27;5:23
pubmed: 18752667
Neuropharmacology. 2006 Mar;50(4):512-20
pubmed: 16378626
Clin Chem. 1998 May;44(5):991-1001
pubmed: 9590372
Am J Physiol Gastrointest Liver Physiol. 2011 Apr;300(4):G538-46
pubmed: 21252045
Bioorg Med Chem Lett. 2012 Oct 1;22(19):6218-23
pubmed: 22926069
Cell Metab. 2017 Aug 1;26(2):310-323
pubmed: 28712655
Cell. 2008 Oct 31;135(3):561-71
pubmed: 18984166
Diabetes. 2006 Aug;55(8):2318-23
pubmed: 16873696
Mol Metab. 2014 Oct 24;4(1):3-14
pubmed: 25685685
PLoS One. 2016 Jun 20;11(6):e0157298
pubmed: 27322810
Mol Metab. 2013 Sep 04;2(4):376-92
pubmed: 24327954
J Clin Endocrinol Metab. 1973 Nov;37(5):826-8
pubmed: 4749457
Horm Metab Res. 1984 May;16(5):226-9
pubmed: 6376308
Cell Metab. 2008 Dec;8(6):532-9
pubmed: 19041768
Metabolism. 2016 Dec;65(12):1706-1719
pubmed: 27832859
Diabetologia. 2013 Dec;56(12):2688-96
pubmed: 24045836
PLoS One. 2016 Nov 22;11(11):e0166758
pubmed: 27875537
Nutrients. 2018 Apr 08;10(4):
pubmed: 29642492
Diabetologia. 2016 Oct;59(10):2156-65
pubmed: 27390011
J Clin Endocrinol Metab. 2014 Sep;99(9):3275-84
pubmed: 24926954
ACS Med Chem Lett. 2013 May 01;4(9):829-34
pubmed: 24900757
Endocrinology. 2009 Jun;150(6):2577-85
pubmed: 19213833
Mol Nutr Food Res. 2012 May;56(5):753-60
pubmed: 22648622
Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E550-9
pubmed: 16219666
Br J Pharmacol. 2008 Mar;153(6):1272-80
pubmed: 18223666
Bioorg Med Chem Lett. 2012 Sep 15;22(18):5942-7
pubmed: 22884988
Endocrinology. 2012 Jul;153(7):3054-65
pubmed: 22685263
Diabetes. 2011 Dec;60(12):3103-9
pubmed: 21984584
J Physiol. 2012 Jun 15;590(12):2917-36
pubmed: 22495587
Methods Mol Biol. 2013;945:319-28
pubmed: 23097115
Diabetologia. 2009 Feb;52(2):289-298
pubmed: 19082577
Cell Metab. 2016 Oct 11;24(4):593-607
pubmed: 27667667
Diabetes Ther. 2016 Mar;7(1):1-9
pubmed: 26965024
Int J Obes (Lond). 2017 Nov;41(11):1693-1701
pubmed: 28792489