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Elucidation of roles of metabolic disorder in proximal tubules and its sensor in progression of diabetic nephropathy

Research Project

Project/Area Number 18K11129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionKochi University

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)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
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)
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
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.

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。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes2020

    • Author(s)
      Funakoshi S, Yoshimura K, Hirano S, Ohmi S, Amano E, Fukuda Y, Terada Y, Fujimoto S
    • Journal Title

      Diabetol Metab Syndr

      Volume: 12 Issue: 1

    • DOI

      10.1186/s13098-020-00579-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel mechanism of impaired metabolism-secretion coupling in β-cells: Loss of cytosolic adenosine triphosphate by leakage (Commentary)2019

    • Author(s)
      Fujimoto S
    • Journal Title

      J Diabetes Investig

      Volume: 10 Issue: 6 Pages: 1401-1404

    • DOI

      10.1111/jdi.13094

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Kidney Int.

      Volume: 93 Issue: 3 Pages: 599-614

    • DOI

      10.1016/j.kint.2017.09.017

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fasting plasma mannose levels are associated with insulin sensitivity independent of BMI in Japanese individuals with diabetes.2018

    • Author(s)
      Amano E, Funakoshi S, Yoshimura K, Hirano S, Ohmi S, Takata H, Terada Y, Fujimoto S
    • Journal Title

      Diabetol Metab Syndr

      Volume: 10 Issue: 1

    • DOI

      10.1186/s13098-018-0391-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Undercarboxylated osteocalcin is correlated with insulin secretion in Japanese individuals with diabetes2019

    • Author(s)
      Funakoshi S, Ohmi S, Amano E, Terada Y, Fujimoto S
    • Organizer
      American Diabetes Association, 79th Scientific Sessions
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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