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Selective peroxisome proliferator-activated receptor-α modulator K-877 regulates the expression of ATP-binding cassette transporter A1 in pancreatic beta cells
https://kagawa-u.repo.nii.ac.jp/records/423
https://kagawa-u.repo.nii.ac.jp/records/4235c229397-e4e8-47b3-9435-555e0776dafd
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本文 (3.1 MB)
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内容の要旨 (64.4 kB)
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審査の結果の要旨 (419.8 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-05-21 | |||||
| タイトル | ||||||
| タイトル | Selective peroxisome proliferator-activated receptor-α modulator K-877 regulates the expression of ATP-binding cassette transporter A1 in pancreatic beta cells | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 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 | |||||
| 著者 |
董, 涛
× 董, 涛 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Abstract ATP-binding cassette transporter A1 (ABCA1) protein is a pivotal regulator of cholesterol and phospholipid efflux from cells to high-density lipoprotein (HDL) particles. Pancreatic ABCA1 functions in beta cell cholesterol homeostasis and affects insulin secretion. We investigated the effect of pemafibrate (K-877), a novel selective PPARα modulator (SPPARMα), on pancreatic ABCA1 expression. In vivo experiment, mice were divided into four treatment groups, namely, normal food plus placebo, high fat diet (HFD) plus placebo, normal food plus K-877 (0.3 mg/kg/day), or HFD plus K-877 (0.3 mg/kg/day), and treated for eight weeks. The results in vitro experiment indicate that K-877 treatment increased levels of ABCA1 mRNA, as well as protein, subsequently reduced the cellular cholesterol content in INS-1 cells. PPARα specific antagonist GW6471 attenuate K-877 induced ABCA1 expression in INS-1 cells. ABCA1 promoter activity increased with K-877 treatment at concentration 1 μM and 10 μM. Glucose-stimulated insulin secretion was ameliorated by K-877 treatment in INS-1 cells and isolated mouse islets. Although the expression of ABCA1 was reduced in mice with HFD treatment, both ABCA1 protein and mRNA levels were increased in mice with K-877 treatment. K-877 treatment improved glucose intolerance induced by HFD in mice. These findings raise the possibility that K-877 may affect insulin secretion by controlling ABCA1 expression in pancreatic beta cells. |
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| 言語 | en | |||||
| 学位名 | ||||||
| 言語 | ja | |||||
| 学位名 | 博士（医学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 16201 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 香川大学 | |||||
| 言語 | en | |||||
| 学位授与機関名 | Kagawa University | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-03-24 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第736号 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | Copyright © 2018 Elsevier B.V. All rights reserved. | |||||
| 権利 | ||||||
| 言語 | ja | |||||
| 権利情報 | この博士論文の本文については、次のエルゼビアの著作権ポリシーの規定により公開しています。「博士論文の場合は、エンバーゴ期間に関係なく機関リポジトリに出版社版を公開することができます。」 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | The text of this doctoral dissertation is published according to the following Elsevier copyright policy. "In the case of doctoral dissertations, publishers can be published in institutional repositories regardless of the Embargo period." | |||||
| 論文ID（NAID） | ||||||
| 識別子タイプ | NAID | |||||
| 関連識別子 | 500001380878 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 30201376 | |||||
| 関連サイト | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.ejphar.2018.09.015 | |||||
| 関連サイト | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://dl.ndl.go.jp/pid/11498634 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | P | |||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | PPARα | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | K-877 | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Cholesterol | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | ABCA1 | |||||
| KEID | ||||||
| 値 | 28979 | |||||
