{"created":"2023-06-19T10:43:40.527178+00:00","id":3944,"links":{},"metadata":{"_buckets":{"deposit":"b30079c7-c322-4ad4-81ca-1677504d5dc2"},"_deposit":{"created_by":11,"id":"3944","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"3944"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00003944","sets":["10:37"]},"author_link":[],"item_6_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"419.e6","bibliographicPageStart":"404","bibliographicVolumeNumber":"32","bibliographic_titles":[{"bibliographic_title":"Cell metabolism","bibliographic_titleLang":"en"}]}]},"item_6_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"富田, 一聖","creatorNameLang":"ja"}]}]},"item_6_date_granted_70":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2021-03-09"}]},"item_6_degree_grantor_68":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"滋賀医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"14202","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_6_degree_name_67":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_6_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"pdf","subitem_description_type":"Other"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"SGLT2 inhibitors offer strong renoprotection in subjects with diabetic kidney disease (DKD). But the mechanism for such protection is not clear. Here, we report that in damaged proximal tubules of high-fat diet-fed ApoE-knockout mice, a model of non-proteinuric DKD, ATP production shifted from lipolysis to ketolysis dependent due to hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). We further found that empagliflozin raised endogenous ketone body (KB) levels, and thus its use or treatment with 1,3-butanediol, a KB precursor, prevented decreases in renal ATP levels and organ damage in the mice. The renoprotective effect of empagliflozin was abolished by gene deletion of Hmgcs2, a rate-limiting enzyme of ketogenesis. Furthermore, KBs attenuated mTORC1-associated podocyte damage and proteinuria in diabetic db/db mice. Our findings show that SGLT2 inhibition-associated renoprotection is mediated by an elevation of KBs that in turn corrects mTORC1 hyperactivation that occurs in non-proteinuric and proteinuric DKD.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_6_description_42":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Thesis or Dissertation","subitem_description_type":"Other"}]},"item_6_description_69":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_description":"令和2年度","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_6_dissertation_number_71":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第899号"}]},"item_6_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier B.V. ","subitem_publisher_language":"en"}]},"item_6_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"32726607","subitem_relation_type_select":"PMID"}}]},"item_6_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1016/j.cmet.2020.06.020"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.cmet.2020.06.020","subitem_relation_type_select":"DOI"}}]},"item_6_relation_48":{"attribute_name":"関係URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"博士論文要旨"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://hdl.handle.net/10422/00012998","subitem_relation_type_select":"HDL"}}]},"item_6_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2020 Elsevier Inc. All rights reserved. "}]},"item_6_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1932-7420","subitem_source_identifier_type":"EISSN"}]},"item_6_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"TOMITA, Issei","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-07-13"}],"displaytype":"detail","filename":"j.cmet.2020.06.020.pdf","filesize":[{"value":"8.1 MB"}],"format":"application/pdf","licensefree":"© 2020 Elsevier Inc. All rights reserved. ","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"j.cmet.2020.06.020","objectType":"fulltext","url":"https://shiga-med.repo.nii.ac.jp/record/3944/files/j.cmet.2020.06.020.pdf"},"version_id":"b8180006-c9be-47cc-ab32-f8e0ac3ae51c"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"diabetic kidney disease","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"atherosclerosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ketone body","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"SGLT2 inhibitor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"lipolysis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"ketolysis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"mTORC1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"nutrient-sensing signal","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"renal energy","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"metabolism","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition.","subitem_title_language":"en"}]},"item_type_id":"6","owner":"11","path":["37"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-07-13"},"publish_date":"2021-07-13","publish_status":"0","recid":"3944","relation_version_is_last":true,"title":["SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition."],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-09-15T05:18:25.179686+00:00"}