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Elucidation of mechanism by which low protein diet suppresses progression of diabetic nephropathy through activation of autophagy in tubular cells

Research Project

Project/Area Number 24591218
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionKanazawa Medical University

Principal Investigator

KITADA Munehiro  金沢医科大学, 医学部, 准教授 (40434469)

Co-Investigator(Kenkyū-buntansha) KOYA Daisuke  金沢医科大学, 医学部, 教授 (70242980)
Co-Investigator(Renkei-kenkyūsha) KUME Shinji  滋賀医科大学, 医学部, 特任助教 (00452235)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords糖尿病腎症 / 低たんぱく質食 / オートファジー / mTOR / たんぱく質制限 / ミトコンドリア / 尿細管 / 炎症 / オートファジー / 栄養応答シグナル / サーチュイン / 糖尿病性腎症 / たんぱく質制限食
Outline of Final Research Achievements

In proximal tubule cells of Wistar fatty (fa/fa) rats, type 2 diabetes model, mitochondrial dysfunction such as fragmentation and swelling, oxidative stress and inflammation due to impairment of autophagy by activation of a mammalian target of rapamycin complex1 (mTORC1) exist, resulting in renal injuries including tubule-interstitial fibrosis, tubular cell injuries and apoptosis and decline of renal function. Advanced low-protein diet (including 5% protein) exhibits the tubule cell protective effects through reduction of mTORC1 activation and restoration of autophagy machinery, leading to suppression of progression of renal dysfunction.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (13 results)

All 2015 2014 2013 2012

All Journal Article (10 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (3 results)

  • [Journal Article] Role of sirtuins in kidney disease.2014

    • Author(s)
      Kitada M, Kume S, Koya D.
    • Journal Title

      Curr Opin Nephrol Hypertens.

      Volume: 23 Issue: 1 Pages: 75-79

    • DOI

      10.1097/01.mnh.0000437330.85675.ac

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical therapeutic strategies for early stage of diabetic kidney disease.2014

    • Author(s)
      Kitada M, Kanasaki K, Koya D
    • Journal Title

      World J Diabetes.

      Volume: 5 Issue: 3 Pages: 342-356

    • DOI

      10.4239/wjd.v5.i3.342

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sirtuins and renal diseases: relationship with aging and diabetic nephropathy2013

    • Author(s)
      Kitada M.
    • Journal Title

      Clin Sci (Lond)

      Volume: 124(3) Issue: 3 Pages: 153-64

    • DOI

      10.1042/cs20120190

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-aging molecule, Sirt1: a novel therapeutic target for diabetic nephropathy2013

    • Author(s)
      Kume S.
    • Journal Title

      Arch Pharm Res.

      Volume: 36(2) Issue: 2 Pages: 230-6

    • DOI

      10.1007/s12272-013-0019-4

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] irtuins as possible drug targets in type 2 diabetes.2013

    • Author(s)
      Kitada M, Kume S, Kanasaki K, Takeda-Watanabe A, Koya D
    • Journal Title

      Curr Drug Targets.

      Volume: 14(6) Pages: 622-636

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with altering autophagy-associated molecules.2013

    • Author(s)
      Xu L, Kanasaki M, He J, Kitada M, Nagao K, Jinzu H, Noguchi Y, Maegawa H, Kanasaki K, Koya D.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1832(10) Issue: 10 Pages: 1605-1612

    • DOI

      10.1016/j.bbadis.2013.05.003

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Calorie restriction in overweight males ameliorates obesity-related metabolic alterations and cellular adaptations through anti-aging effects, possibly including AMPK and SIRT1 activation.2013

    • Author(s)
      Kitada M, Kume S, Takeda-Watanabe A, Tsuda S, Kanasaki K, Koya D.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1830(10) Issue: 10 Pages: 4820-4827

    • DOI

      10.1016/j.bbagen.2013.06.014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential.2013

    • Author(s)
      Kitada M, Koya D.
    • Journal Title

      Diabetes Metab J.

      Volume: 37(5) Pages: 315-325

    • Related Report
      2013 Research-status Report
  • [Journal Article] Renal protective effects of resveratrol.2013

    • Author(s)
      Kitada M, Koya D.
    • Journal Title

      Oxid Med Cell Longev.

      Volume: 2013 Pages: 1-7

    • DOI

      10.1155/2013/568093

    • NAID

      40019560561

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The use of calorie restriction mimetics to study aging.2013

    • Author(s)
      Kitada M, Koya D.
    • Journal Title

      Methods Mol Biol.

      Volume: 1048 Pages: 95-107

    • DOI

      10.1007/978-1-62703-556-9_8

    • ISBN
      9781627035552, 9781627035569
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] たんぱく質制限による2型糖尿病腎尿細管におけるミトコンドリアの断片化と融合バランスの是正と腎保護効果2015

    • Author(s)
      北田宗弘
    • Organizer
      日本腎臓学会年次学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-06-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] たんぱく質制限の2型糖尿病ラット腎症に対する腎保護効果2015

    • Author(s)
      北田宗弘
    • Organizer
      日本糖尿病学会年次学術集会
    • Place of Presentation
      海峡メッセ他(山口県下関市)
    • Year and Date
      2015-05-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 2型糖尿病腎症における高度たんぱく質制限の腎保護効果と糖・脂質代謝への影響2012

    • Author(s)
      北田宗弘
    • Organizer
      日本腎臓学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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