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タイトル: | JTP-109192, a novel G protein-coupled receptor 119 agonist, prevents atherosclerosis by improving hypercholesterolemia in congenic spontaneously hyperlipidaemic mice |
著者: | Tadaki, Hironobu Ogawa, Naoto Yamanaka, Masao Motohashi, Yu Sasase, Tomohiko Kawai, Takashi Toriniwa, Yasufumi Fukuda, Sumiaki Ogawa, Nobuya Harada, Kazuhito Ohta, Takeshi Yamada, Takahisa |
著者名の別形: | 太田, 毅 |
キーワード: | atherosclerosis dyslipidaemia G protein‐coupled receptor 119 spontaneously hyperlipidaemic mouse |
発行日: | Mar-2021 |
出版者: | Wiley |
誌名: | Clinical and Experimental Pharmacology and Physiology |
巻: | 48 |
号: | 3 |
開始ページ: | 381 |
終了ページ: | 388 |
抄録: | 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. |
著作権等: | This is the peer reviewed version of the following article: Tadaki, H, Ogawa, N, Yamanaka, M, et al. JTP‐109192, a novel G protein‐coupled receptor 119 agonist, prevents atherosclerosis by improving hypercholesterolaemia in congenic spontaneously hyperlipidaemic mice. Clin Exp Pharmacol Physiol. 2021; 48: 381– 388, which has been published in final form at https://doi.org/10.1111/1440-1681.13423. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. The full-text file will be made open to the public on 4 November 2021 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/261718 |
DOI(出版社版): | 10.1111/1440-1681.13423 |
PubMed ID: | 33068442 |
出現コレクション: | 学術雑誌掲載論文等 |
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