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KAKEN_17K09710seika.pdf
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Title |
Title |
マスイメージングによる腎代謝産物の解析に基づくSGLT2阻害薬の腎保護効果の解明
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マス イメージング ニ ヨル ジンタイシャ サンブツ ノ カイセキ ニ モトズク SGLT2 ソガイヤク ノ ジン ホゴ コウカ ノ カイメイ
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Masu imējingu ni yoru jintaisha sanbutsu no kaiseki ni motozuku SGLT2 sogaiyaku no jin hogo kōka no kaimei
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Elucidation of renoprotective effects of an SGLT2 inhibitor through analysis of renal energy metabolism by an imaging mass spectrometry
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萩原, あいか
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ハギワラ, アイカ
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Hagiwara, Aika
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慶應義塾大学・医学部 (信濃町) ・共同研究員
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Research team head
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科研費研究者番号 : 00627052
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宮下, 和季
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ミヤシタ, カズトシ
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Miyashita, Kazutoshi
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Affiliation |
慶應義塾大学・医学部・特任講師
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Research team member
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科研費研究者番号 : 50378759
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伊藤, 裕
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イトウ, ヒロシ
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Itō, Hiroshi
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慶應義塾大学・医学部・教授
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Research team member
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科研費研究者番号 : 40252457
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2020
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科学研究費補助金研究成果報告書
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2019
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マスイメージングによる腎代謝産物の可視化解析を行った結果、SGLT2阻害薬による尿糖増加に伴う腎糖低下が腎臓全体のエネルギー代謝を変容させ、解糖系中間代謝産物、アセチルCoAおよびTCA回路の低下、ATP低下およびアデノシン上昇をきたし、腎自律神経求心路を介して全身のエネルギー代謝にも影響を与える可能性が示唆された。またキサンチンオキシダーゼ阻害薬は腎血流不足に伴うATP低下をアデニル酸再合成の促進によって緩和し、腎保護効果を発揮する可能性が示唆された。以上の結果をふまえ、慢性腎臓病において、代謝変容の観点からの新規腎保護戦略の提案を目指す。
Metabolome analysis revealed a decrease in ATP level in the kidneys of tofogliflozin-treated mice and an increase in ATP degradation products, including adenosine. Direct injection of adenosine in the renal artery induced activation of HSL in the white and brown adipose tissues. These results indicate that the renal afferent nerves mediate the lipolytic effect of an SGLT2 inhibitor in obese mice. The alterations to the renal energy metabolism can play significant roles in the lipolysis through the renal afferent nerves and body weight reduction by tofogliflozin. An xanthine oxidase inhibitor, febuxostat, which blocks the degradation pathway of adenine nucleotides, promoted ATP recovery and exerted renoprotective effects in the postischemic kidney. These findings suggest a novel therapeutic approach for the chronic kidney disease through modification of renal metabolism.
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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2017~2019
課題番号 : 17K09710
研究分野 : 腎臓内分泌代謝内科学
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Mar 5, 2021 | | インデックス を変更 |
Nov 14, 2022 | | Creator Name,Creator Kana,Creator Romanization,Creator Affiliation,Creator Affiliation (Translated),Creator Role,Creator Link,Abstract 内容,Note 注記 を変更 |
Apr 12, 2024 | | Creator を変更 |
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