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Tubular Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin : A Possible Role of HIF-1α Expression and Oxygen Metabolism
https://asahikawa-med.repo.nii.ac.jp/records/4037
https://asahikawa-med.repo.nii.ac.jp/records/4037e6e0b9ac-4665-471d-a70b-b1f3079ab00f
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
4490.pdf (1.5 MB)
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| Item type | 学術雑誌論文 / Journal Article_02(1) | |||||
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| 公開日 | 2012-05-17 | |||||
| タイトル | ||||||
| タイトル | Tubular Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin : A Possible Role of HIF-1α Expression and Oxygen Metabolism | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
滝山, 由美
× 滝山, 由美× Harumi, Tatsuo× Watanabe, Jun× Fujita, Yukihiro× Honjo, Jun× Shimizu, Norihiko× Makino, Yuichi× Haneda, Masakazu |
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| 書誌情報 |
Diabetes 巻 60, 号 3, p. 981-992, 発行日 2011-03-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 0012-1797 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.2337/db10-0655 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | OBJECTIVE : Chronic hypoxia has been recognized as a key regulator in renal tubulointerstitial fibrosis, as seen in diabetic nephropathy, which is associated with the activation of hypoxia-inducible factor (HIF)-1α. We assess here the effects of the biguanide, metformin, on the expression of HIF-1α in diabetic nephropathy using renal proximal tubular cells and type 2 diabetic rats. RESEARCH DESIGN AND METHODS : We explored the effects of metformin on the expression of HIF-1α using human renal proximal tubular epithelial cells (HRPTECs). Male Zucker diabetic fatty (ZDF; Gmi-fa/fa) rats were treated from 9 to 39 weeks with metformin (250 mg/kg^<−1>/day^<−1>) or insulin. RESULTS : Metformin inhibited hypoxia-induced HIF-1α accumulation and the expression of HIF-1–targeted genes in HRPTECs. Although metformin activated the downstream pathways of AMP-activated protein kinase (AMPK), neither the AMPK activator, AICAR, nor the mTOR inhibitor, rapamycin, suppressed hypoxia-induced HIF-1α expression. In addition, knockdown of AMPK-α did not abolish the inhibitory effects of metformin on HIF-1α expression. The proteasome inhibitor, MG-132, completely eradicated the suppression of hypoxia-induced HIF-1α accumulation by metformin. The inhibitors of mitochondrial respiration similarly suppressed hypoxia-induced HIF-1α expression. Metformin significantly decreased ATP production and oxygen consumption rates, which subsequently led to increased cellular oxygen tension. Finally, metformin, but not insulin, attenuated tubular HIF-1α expression and pimonidazole staining and ameliorated tubular injury in ZDF rats. CONCLUSIONS : Our data suggest that hypoxia-induced HIF-1α accumulation in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxygen consumption. | |||||
| 言語 | en | |||||
| 注記 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | http://dx.doi.org/10.2337/db10-0655 | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | text | |||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| ID(XooNIps) | ||||||
| 値 | 21282369 | |||||
| 閲覧数(XooNIps) | ||||||
| 値 | 1008 | |||||
| ダウンロード数(XooNIps) | ||||||
| 値 | 962 | |||||
