The pathophysiology of diabetic tubulopathy and therapeutic application
| Project/Area Number |
16H05315
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
Wakino Shu 慶應義塾大学, 医学部(信濃町), 准教授 (50265823)
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| Co-Investigator(Kenkyū-buntansha) |
長谷川 一宏 慶應義塾大学, 医学部(信濃町), 助教 (30424162)
伊藤 裕 慶應義塾大学, 医学部(信濃町), 教授 (40252457)
徳山 博文 慶應義塾大学, 医学部(信濃町), 講師 (50276250)
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| Research Collaborator |
MURAOKA Hirokazu
UMINO Hiroyuki
NAITOH Makiko
KANDA Takeshi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 糖尿病性腎錠 / 近位尿細管 / Rho / Sirtuin / PHD2 / SGLT2 / 尿細管細胞肥大 / mDia / 近位尿細管肥大 / NAD / NMN / 超早期治療介入 / 糖尿病性腎臓病 / 糖尿病性腎症 / 肥満関連腎症 / iNAMPT / 内科 / 糖尿病 / 臨床 / 薬理学 / シグナル伝達 / ニコチン酸代謝 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
We have investigated the pathogenesis of Diabetic tubulopathy that is tubular damages or disfunction in the diabetic subjects. First, we identified the activation of the functional protein in the proximal tubular cells including small G protein Rho, tissue oxygen sensor PHD2, NAD-dependent deacetylase Sirt1 and glucose transported, SGLT2 in the very early stage in diabetes. We also found that proximal tubular cell hypertrophy as the early histological abnormalities in diabetes. We finally examined the intervention to these proteins by the amelioration of early activation of these molecules and found that the early treatment with statin or NAD intermediate, NMN mitigated diabetic albuminuria.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病性腎臓病は現在新規透析導入の原因疾患の第1位であり、透析導入の6割近い患者は糖尿病が原因である。その治療体系は、血糖管理、脂質管理、血圧管理といったリスクファクター管路のみで腎臓自体をターゲットにした治療法がない状況である。糖尿病はエネルギー代謝異常の疾患である故エネルギー代謝の活発な近位尿細管が真っ先に障害されるという考えのもと近位尿細管における超早期の機能異常に注目した病態解明、治療戦略の構築を目指し、スタチン大量投与、NMN大量投与などを提唱したいと考えている。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Obesity-induced kidney injury is attenuated by amelioration of aberrant PHD2 activation in proximal tubules2016
Author(s)
Futatsugi K, Tokuyama H, Shibata S, Naitoh M, Kanda T, Minakuchi H, Yamaguchi S, Hayashi K, Minamishima YA, Yanagita M, Wakino S, Itoh H
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 365331-12
DOI
Related Report
Peer Reviewed / Open Access
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