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グルコーススパイクとインスリン抵抗性は相乗的に内皮機能を障害しバルドキソロンメチルは内皮障害を減弱する
http://hdl.handle.net/10232/00032018
http://hdl.handle.net/10232/00032018f71c6850-c2d3-418a-a961-1b1cfe78b94e
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Diss_小木曽_和磨_ISK660_2022 (3.4 MB)
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Abstract_小木曽_和磨_4517800038_2022 (64.2 kB)
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Result_Ogiso_kazuma_isk_660. (122.9 kB)
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Comments_Ogiso_kazuma_isk_660 (55.8 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-06-13 | |||||
| タイトル | ||||||
| タイトル | Repeated Glucose Spikes and Insulin Resistance Synergistically Deteriorate Endothelial Function and Bardoxolone Methyl Ameliorates Endothelial Dysfunction | |||||
| タイトル言語 | en | |||||
| タイトル | ||||||
| タイトル | グルコーススパイクとインスリン抵抗性は相乗的に内皮機能を障害しバルドキソロンメチルは内皮障害を減弱する | |||||
| タイトル言語 | ja | |||||
| 著者 |
小木曽, 和磨
× 小木曽, 和磨 |
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| 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 | |||||
| 要約 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Background: Both insulin resistance and postprandial glucose spikes are known for their potential to induce vascular endothelial dysfunction in individuals with metabolic syndrome. However, these factors are inextricable, and therefore, their relative contributions to inducing endothelial dysfunction remain elusive. In this study, we aimed to disentangle the effects of these factors and clarify whether bardoxolone methyl (CDDO-Me), a novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator, protects against glucose spike-induced endothelial dysfunction. Methods: We induced glucose spikes twice daily for a duration of 1 week to rats fed a standard/control diet (CD) and Western-type diet (WTD). Endothelium-dependent relaxation (EDR) was evaluated using isolated thoracic aortas. Gene expression and dihydroethidium (DHE)-fluorescence studies were carried out; the effect of CDDO-Me on aortic endothelial dysfunction in vivo was also evaluated. Results: Neither WTD-induced insulin resistance nor pure glucose spikes significantly deteriorated EDR. However, under high-glucose (20 mM) conditions, the EDR of thoracic aortas of WTD-fed rats subjected to glucose spikes was significantly impaired. In this group of rats, we observed significantly enhanced DHE fluorescence as a marker of reactive oxygen species, upregulation of an oxidative stress-related gene (NOX2), and downregulation of an antioxidant gene (SOD2) in the thoracic aortas. As expected, treatment of the thoracic aorta of this group of rats with antioxidant agents significantly improved EDR. We also noted that pretreatment of aortas from the same group with CDDO-Me attenuated endothelial dysfunction, accompanied by a correction of the redox imbalance, as observed in gene expression and DHE fluorescence studies. Conclusions: For the first time, we showed that insulin resistance and glucose spikes exert a synergistic effect on aortic endothelial dysfunction. Furthermore, our study reveals that CDDO-Me ameliorates endothelial dysfunction caused by glucose spikes in a rat model of metabolic syndrome. Kazuma Ogiso, Sigfrid Casmir Shayo, Shigeru Kawade, Hiroshi Hashiguchi, Takahisa Deguchi, Yoshihiko Nishio Repeated glucose spikes and insulin resistance synergistically deteriorate endothelial function and bardoxolone methyl ameliorates endothelial dysfunction PLOS ONE 2022 https://doi.org/10.1371/journal.pone.0263080 |
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| 内容記述言語 | en | |||||
| 作成日 | ||||||
| 日付 | 2022-05-17 | |||||
| 日付タイプ | Collected | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| NDC | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 490 | |||||
| ファイル（説明） | ||||||
| 内容記述 | 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨 | |||||
| 公開者・出版者 | ||||||
| 出版者 | PLOS | |||||
| 出版者言語 | en | |||||
| 公開者・出版者 | ||||||
| 出版者 | 鹿児島大学 | |||||
| 出版者言語 | ja | |||||
| 公開者・出版者 | ||||||
| 出版者 | カゴシマ ダイガク | |||||
| 出版者言語 | ja-Kana | |||||
| 備考 | ||||||
| 備考 | 【指導教員:西尾善彦】 | |||||
| date.appl | ||||||
| appl | 【学位申請日】2022-03-02 | |||||
| 学位名 | ||||||
| 学位名の言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位名 | ||||||
| 学位名の言語 | en | |||||
| 学位名 | Doctor of Philosophy in Medical Science | |||||
| 学位授与機関名 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17701 | |||||
| 学位授与機関名の言語 | ja | |||||
| 学位授与機関名 | 鹿児島大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2022-05-30 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲総研第660号 | |||||
