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Effect of TNF-α on the expression of ABCA1 in pancreatic β-cells
https://kagawa-u.repo.nii.ac.jp/records/347
https://kagawa-u.repo.nii.ac.jp/records/34727a8600d-c618-4685-a401-2c6e0afbcf43
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本文 (1.2 MB)
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内容の要旨 (70.3 kB)
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審査の結果の要旨 (91.5 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2019-12-16 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Effect of TNF-α on the expression of ABCA1 in pancreatic β-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 |
佐藤, 誠祐
× 佐藤, 誠祐
WEKO
943
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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), a 254-kD membrane protein, is a key regulator of lipid efflux from cells to apolipoproteins. ABCA1 in pancreatic β-cells influences insulin secretion and cholesterol homeostasis. Tumor necrosis factor (TNF)-α is a pleiotropic cytokine that elicits a wide spectrum of physiological events, including cell proliferation, differentiation and apoptosis and is also known to decrease glucose-dependent insulin secretion in pancreatic islets. In the present study, we examined the role of TNF-α on ABCA1 expression in rat pancreatic islets and INS-1 cells. ABCA1 protein levels decreased in response to rising concentrations of TNF-α in pancreatic islets. Real-time polymerase chain reaction analysis showed a significant decrease in ABCA1 mRNA expression. In parallel with its effect on endogenous ABCA1 mRNA levels, TNF-α suppressed the activity of a reporter construct containing the ABCA1 promoter. This effect was abrogated by BIRB796, but not by SB203580 or LY-294002. The constitutively active form of p38 mitogen-activated protein kinase (MAPK) γ suppressed ABCA1 promoter activity but not p38-MAPK (α, β), while a dominant-negative mutant of p38-MAPK γ blocked the effect of TNF-α on ABCA1 promoter activity. BIRB796 inhibited the increased cholesterol ester content induced by TNF-α. However, BIRB796 had no effect on either the decreased insulin content or the ABCA1 suppression caused by TNF-α in INS-1 cells. We checked the influence of TNF-α of insulin secretion and glucose-stimulated insulin secretion in rat pancreatic islet and INS-1 cell. TNF-α suppressed the insulin secretion and glucose-stimulated insulin secretion in both rat pancreatic islet and INS-1 cell. In summary, TNF-α suppressed the expression of endogenous ABCA1 and suppress the insulin secretion in pancreatic islets and INS-1 cells. These findings raise the possibility that TNF-α may affect insulin secretion by controlling ABCA1 expression. |
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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 | 2018-12-26 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第700号 | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | Copyright: © 2018 Society for Endocrinology 2018 | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | Copyright © 2019 Bioscientifica Ltd | |||||||||||
| 権利 | ||||||||||||
| 言語 | ja | |||||||||||
| 権利情報 | エンバーゴ期間満了 / The embargo period has expired | |||||||||||
| 論文ID（NAID） | ||||||||||||
| 識別子タイプ | NAID | |||||||||||
| 関連識別子 | 500001368085 | |||||||||||
| PubMed番号 | ||||||||||||
| 識別子タイプ | PMID | |||||||||||
| 関連識別子 | 30131353 | |||||||||||
| 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/10.1530/jme-18-0167 | |||||||||||
| 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/11433658 | |||||||||||
| 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 | tumor necrosis factor-α | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | ATP-binding cassette transporter A1 | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | p38MAPK | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | pancreatic β cells | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | cholesterol accumulation | |||||||||||
| KEID | ||||||||||||
| 値 | 28576 | |||||||||||
