JTP-109192, a novel G protein-coupled receptor 119 agonist, prevents atherosclerosis by improving hypercholesterolemia in congenic spontaneously hyperlipidaemic mice
| Autor: | Takahisa Yamada, Kazuhito Harada, Takashi Kawai, Tomohiko Sasase, Yu Motohashi, Sumiaki Fukuda, Nobuya Ogawa, Masao Yamanaka, Naoto Ogawa, Hironobu Tadaki, Yasufumi Toriniwa, Takeshi Ohta |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Agonist dyslipidaemia Physiology medicine.drug_class Hypercholesterolemia Congenic Carbohydrate metabolism Pharmacology Receptors G-Protein-Coupled 03 medical and health sciences Oleoylethanolamide chemistry.chemical_compound Mice 0302 clinical medicine Physiology (medical) Insulin-Secreting Cells Insulin Secretion medicine Animals Hypoglycemic Agents Receptor G protein‐coupled receptor 119 G protein-coupled receptor Cholesterol business.industry spontaneously hyperlipidaemic mouse 030104 developmental biology GPR119 chemistry Diabetes Mellitus Type 2 030220 oncology & carcinogenesis atherosclerosis business |
| Zdroj: | Clinical and Experimental Pharmacology and Physiology. 48(3):381-388 |
| ISSN: | 0305-1870 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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