{"created":"2023-06-19T11:23:29.331049+00:00","id":4037,"links":{},"metadata":{"_buckets":{"deposit":"13563233-4025-4ddd-a753-3c130957fbe7"},"_deposit":{"created_by":3,"id":"4037","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"4037"},"status":"published"},"_oai":{"id":"oai:asahikawa-med.repo.nii.ac.jp:00004037","sets":["7","7:24"]},"author_link":["12271","12272","12273","12274","12275","12276","12277","12278"],"item_5_biblio_info_21":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2011-03-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"992","bibliographicPageStart":"981","bibliographicVolumeNumber":"60","bibliographic_titles":[{"bibliographic_title":"Diabetes"}]}]},"item_5_description_33":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_5_description_36":{"attribute_name":"注記","attribute_value_mlt":[{"subitem_description":"http://dx.doi.org/10.2337/db10-0655","subitem_description_type":"Other"}]},"item_5_description_37":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"text","subitem_description_type":"Other"}]},"item_5_description_41":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_5_relation_24":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.2337/db10-0655","subitem_relation_type_select":"DOI"}}]},"item_5_source_id_22":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0012-1797","subitem_source_identifier_type":"PISSN"}]},"item_5_text_44":{"attribute_name":"ID(XooNIps)","attribute_value_mlt":[{"subitem_text_value":"21282369"}]},"item_5_text_54":{"attribute_name":"閲覧数(XooNIps)","attribute_value_mlt":[{"subitem_text_value":"1008"}]},"item_5_text_55":{"attribute_name":"ダウンロード数(XooNIps)","attribute_value_mlt":[{"subitem_text_value":"962"}]},"item_5_version_type_38":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"滝山, 由美","creatorNameLang":"ja"},{"creatorName":"タキヤマ, ユミ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"12271","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Harumi, Tatsuo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"12272","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Watanabe, Jun","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"12273","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujita, Yukihiro","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"12274","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Honjo, Jun","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"12275","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shimizu, Norihiko","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"12276","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Makino, Yuichi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"12277","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Haneda, Masakazu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"12278","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-07-06"}],"displaytype":"detail","filename":"4490.pdf","filesize":[{"value":"1.5 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"4490.pdf","url":"https://asahikawa-med.repo.nii.ac.jp/record/4037/files/4490.pdf"},"version_id":"c5df3428-2c0b-4a9f-bfbb-9325310d39b5"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Tubular Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin : A Possible Role of HIF-1α Expression and Oxygen Metabolism","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Tubular Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin : A Possible Role of HIF-1α Expression and Oxygen Metabolism","subitem_title_language":"en"}]},"item_type_id":"5","owner":"3","path":["6","7","24"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2012-05-17"},"publish_date":"2012-05-17","publish_status":"0","recid":"4037","relation_version_is_last":true,"title":["Tubular Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin : A Possible Role of HIF-1α Expression and Oxygen Metabolism"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2024-07-26T08:38:28.727495+00:00"}