TGR5 Activation Modulates an Inhibitory Effect on Liver Fibrosis Development Mediated by Anagliptin in Diabetic Rats.

• 資料種別: 博士論文
• ISSN: 2073-4409
• タイトル: TGR5 Activation Modulates an Inhibitory Effect on Liver Fibrosis Development Mediated by Anagliptin in Diabetic Rats.
• 巻次・部編番号: 8 10
• 著者・編者: Kaya, Daisuke; Kaji, Kosuke; Tsuji, Yuki; Yamashita, Satoko; Kitagawa, Koh; Ozutsumi, Takahiro; Fujinaga, Yukihisa; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 著者標目: Kaya, Daisuke; Kaji, Kosuke; Tsuji, Yuki; Yamashita, Satoko; Kitagawa, Koh; Ozutsumi, Takahiro; Fujinaga, Yukihisa; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 出版事項: MDPI
• 出版年月日等: 2019-09-26; 8 10
• 出版年（W3CDTF）: 2019-09-26
• 並列タイトル等: TGR5活性化はアナグリプチンによる糖尿病ラットに対する肝線維化抑制効果を増強する
• タイトル（掲載誌）: Cells
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2021-03-15
• 授与年月日（W3CDTF）: 2021-03-15
• 報告番号: 甲第766号
• 学位: 博士（医学）
• 博論授与番号: 甲第766号
• 本文の言語コード: eng
• 件名標目: dipeptidyl peptidase-4 inhibitors; hepatic stellate cells; oleanolic acid; Takeda G protein-coupled receptor 5
• 対象利用者: 一般
• 一般注記: type:Thesis; Hyperglycemia and hyperinsulinemia activate the proliferative potential of hepatic stellate cells (HSCs) and promote hepatic fibrosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, antidiabetic agents, reportedly inhibit the HSC proliferation. Additionally, Takeda G protein-coupled receptor 5 (TGR5) agonists induce the systemic release of glucagon-like peptides from intestinal L cells, which maintains glycemic homeostasis. This study assessed the combined effect of TGR5 agonist and DPP-4 inhibitor on diabetes-based liver fibrosis development. Male diabetic rats received intraperitoneal injection of porcine serum (PS) to induce liver fibrosis, and they were orally administered the following agents: oleanolic acid (OA) as a TGR5 agonist, anagliptin (ANA) as a DPP-4 inhibitor, and a combination of both agents. Treatment with OA or ANA significantly improved glycemic status and attenuated intrahepatic steatosis and lipid peroxidation in diabetic rats. PS-induced liver fibrosis development was also drastically suppressed by treatment with either agent, and the combination of both reciprocally enhanced the antifibrotic effect. Fecal microbiome demonstrated that both agents inhibited the increase in the Firmicutes/Bacteroidetes ratio, an indicator of dysbiosis related to metabolic syndromes. Furthermore, ANA directly inhibited in vitro HSC proliferative and profibrogenic activities. Collectively, TGR5 agonist and DPP-4 inhibitor appears to be a novel strategy against liver fibrosis under diabetic conditions.; 博士（医学）・甲第766号・令和3年3月15日; © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).; identifier:Cells Vol.8 No.10 Article No.1153 (2019 Sep); identifier:20734409; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3890; identifier:Cells, 8(10): Article No.1153
• DOI: info:doi/10.3390/cells8101153; https://doi.org/info:doi/10.3390/cells8101153
• 国立国会図書館永続的識別子: info:ndljp/pid/12071090; https://dl.ndl.go.jp/pid/12071090
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2022-02-06T04:33:19+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://hdl.handle.net/10564/3890
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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