Elucidation of roles of metabolic disorder in proximal tubules and its sensor in progression of diabetic nephropathy
| Project/Area Number |
18K11129
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Kochi University |
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Principal Investigator |
Fujimoto Shimpei 高知大学, 教育研究部医療学系臨床医学部門, 教授 (00333576)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 糖尿病 / 腎障害 / 近位尿細管 / ナトリウム・グルコース共役輸送体 / 代謝障害センサー / ミトコンドリア / 糖尿病性腎症 / グルコース再吸収 / ATP産生 / 代謝障害 / グルコース輸送 |
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| Outline of Final Research Achievements |
In proximal tubular epithelial cells (PTEC) in diabetes, increase in glucose and sodium flux through sodium-glucose cotransporter (SGLT) due to increase in urine glucose causes metabolic stress on these cells. Therefore, roles of thioredoxin-interacting protein (TXNIP), a metabolic stress sensor, in PTEC in progression of diabetic nephropathy should be elucidated. In diabetic STZ mice, blood glucose and urinary albumin increased compared to controls. Protein expression of TXNIP increased in skeletal muscle but did not increased in liver and proximal tubules. In STZ mice, oral administration of SGLT2 inhibitor decreased blood glucose and caused decrease in TXNIP expression in skeletal muscles but did not alter TXNIP expression in liver and proximal tubules.
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| Academic Significance and Societal Importance of the Research Achievements |
本研研究においてTXNIPが糖尿病の尿細管における代謝ストレスを感知する役割を担っていることが証明されれば、新たな治療ターゲットが提示でき、医療経済的にも重要課題である透析予防において新規治療戦略の構築に貢献できる可能性があった。しかし実験の結果、その関与は否定的であった。本研究によりTXNIPは骨格筋においては代謝障害センサーとして作動する可能性が示唆されたので、更なる研究がすすめば、糖尿病の病態への理解が深まり、新たな治療戦略の端緒となる可能性がある。
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Report
(5 results)
Research Products
(6 results)
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[Journal Article] Knockout of the interleukin-36 receptor protects against renal ischemia-reperfusion injury by reduction of proinflammatory cytokines2018
Author(s)
Nishikawa H, Taniguchi Y, Matsumoto T, Arima N, Masaki M, Shimamura Y, Inoue K, Horino T, Fujimoto S, Ohko K, Komatsu T, Udaka K, Sano S, Terada Y.
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Journal Title
Kidney Int.
Volume: 93
Issue: 3
Pages: 599-614
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Correlation analysis between insulin sensitivity, branched-chain acid, and adiponectin levels in Japanese individuals with varying degrees of glucose tolerance2020
Author(s)
Amano E, Yoshimura K, Funakoshi S, Hirano S, Ohmi S, Terada Y, Fujimoto S
Organizer
American Diabetes Association, 80th Scientific Sessions, Chicago (On line sessions), IL, USA
Related Report
Int'l Joint Research
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