JTP-109192, a novel G protein-coupled receptor 119 agonist, prevents atherosclerosis by improving hypercholesterolaemia in congenic spontaneously hyperlipidaemic mice.
G protein-coupled receptor 119
atherosclerosis
dyslipidaemia
spontaneously hyperlipidaemic mouse
Journal
Clinical and experimental pharmacology & physiology
ISSN: 1440-1681
Titre abrégé: Clin Exp Pharmacol Physiol
Pays: Australia
ID NLM: 0425076
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
06
03
2020
revised:
25
09
2020
accepted:
14
10
2020
pubmed:
18
10
2020
medline:
15
12
2021
entrez:
17
10
2020
Statut:
ppublish
Résumé
G protein-coupled receptor 119 (GPR119) expression in pancreatic β-cells and intestinal L-cells is a potential therapeutic target for the treatment of type 2 diabetes. Previously, we have reported that the GPR119 agonist JTP-109192 improves glucose metabolism with single and repeated administration. Conversely, overexpression of the Gpr119 gene reportedly regulates cholesterol transporter expression in animal models, and a natural GPR119 agonist, oleoylethanolamide (OEA), improves atherosclerosis. Therefore, improving dyslipidaemia is considered a possible feature of GPR119 agonists. In the present study, the lipid-lowering effect of JTP-109192 was examined in BALB/c background spontaneously hyperlipidaemic (SHL) mice with repeated administration, once daily for 12 weeks. On repeated administration, JTP-109192 revealed a cholesterol-lowering effect and improved atherosclerosis following histopathological examination. With further investigation, the cholesterol-lowering effect and subsequent antiatherosclerotic effect of JTP-109192 was attributed to changes in intestinal cholesterol metabolism gene expression. Based on these results, JTP-109192 represents a new potential antihypercholesterolaemic agent for the treatment of dyslipidaemia.
Identifiants
pubmed: 33068442
doi: 10.1111/1440-1681.13423
doi:
Substances chimiques
Hypoglycemic Agents
0
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
381-388Informations de copyright
© 2020 John Wiley & Sons Australia, Ltd.
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