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Centrally administered GLP-1 analogue improves intestinal barrier function through the brain orexin and the vagal pathway in rats
https://asahikawa-med.repo.nii.ac.jp/records/2000589
https://asahikawa-med.repo.nii.ac.jp/records/20005890ba06ebf-3369-41ff-bcd4-ba054d003f3f
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
K609 Funayama Takuya_TD.pdf (1.4 MB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||||||||
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| 公開日 | 2025-11-19 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Centrally administered GLP-1 analogue improves intestinal barrier function through the brain orexin and the vagal pathway in rats | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Brain | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | GLP-1 | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Leaky gut | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Orexin | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Vagus | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| その他（別言語等）のタイトル | ||||||||||||
| その他のタイトル | GLP-1 analogue 脳室内投与は脳内オレキシンシグナル，および迷走神経を介して腸管バリア機能を改善する | |||||||||||
| 言語 | ja | |||||||||||
| 著者 |
船山, 拓也
× 船山, 拓也
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| bibliographic_information |
en : Brain research 号 1809, p. 148371, 発行日 2023-06-15 |
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| ISSN | ||||||||||||
| 収録物識別子タイプ | PISSN | |||||||||||
| 収録物識別子 | 0006-8993 | |||||||||||
| DOI | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1016/j.brainres.2023.148371 | |||||||||||
| リンクURL | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | https://www.sciencedirect.com/science/article/pii/S0006899323001427 | |||||||||||
| 言語 | en | |||||||||||
| 識別番号 その他 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | PMID: 37076092 | |||||||||||
| 言語 | en | |||||||||||
| dissertation_number | ||||||||||||
| 学位授与番号 | 甲第609号 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2025-03-25 | |||||||||||
| 学位名 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位名 | 博士（医学） | |||||||||||
| item_10_degree_grantor_32 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位授与機関名 | 旭川医科大学 | |||||||||||
| item_10_description_33 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Leaky gut, an altered intestinal barrier function, has been described in many diseases such as irritable bowel syndrome (IBS). We have recently demonstrated that orexin in the brain blocked leaky gut in rats, suggesting that the brain plays a role in regulation of intestinal barrier function. In the present study, we tried to clarify whether GLP-1 acts centrally in the brain to regulate intestinal barrier function and its mechanism. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Intracisternal injection of GLP-1 analogue, liraglutide dose-dependently abolished increased colonic permeability in response to lipopolysaccharide. Either atropine or surgical vagotomy blocked the central GLP-1-induced improvement of colonic hyperpermeability. Intracisternal GLP-1 receptor antagonist, exendin (9-39) prevented the central GLP-1-induced blockade of colonic hyperpermeability. In addition, intracisternal injection of orexin receptor antagonist, SB-334867 blocked the GLP-1-induced improvement of intestinal barrier function. On the other hand, subcutaneous liraglutide also improved leaky gut but larger doses of liraglutide were needed to block it. In addition, neither atropine nor vagotomy blocked subcutaneous liraglutide-induced improvement of leaky gut, suggesting that central or peripheral GLP-1 system works separately to improve leaky gut in a vagal-dependent or independent manner, respectively. These results suggest that GLP-1 acts centrally in the brain to reduce colonic hyperpermeability. Brain orexin signaling and the vagal cholinergic pathway play a vital role in the process. We would therefore suggest that activation of central GLP-1 signaling may be useful for leaky gut-related diseases such as IBS. | |||||||||||
| 言語 | en | |||||||||||
| item_10_description_36 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | Copyright © 2023 Elsevier B.V. All rights reserved. | |||||||||||
| 言語 | en | |||||||||||
| 出版タイプ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
