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Elucidation of role of changing S-adenosylmethionine (SAM) metabolism for the pathogenesis of diabetic kidney disease

Research Project

Project/Area Number 17K09718
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) 古家 大祐  金沢医科大学, 医学部, 教授 (70242980)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords糖尿病性腎臓病 / 2型糖尿病ラット / 低蛋白質食 / メチオニン / S-アデノシルメチオニン / オートファジー / グリシンNメチルトランスフェラーゼ / 糖尿病性腎症 / mTOR1 / 糖尿病腎症 / 糖尿病
Outline of Final Research Achievements

A low-protein diet (LPD) exerts the renoprotective effect through the suppression of mechanistic target of rapamycin complex 1 (mTORC1) and improvement of autophagy in Wistar fatty (fa/fa) rats (WFRs), type 2 diabetes/obesity. Results of metabolome analysis in blood of rats demonstrated that the levels of S-adenosylmethionine (SAM), metabolite of methionine (Met), is clearly increased in the blood of WFRs compared to non-diabetic control rats, and a LPD decreases it. In addition, the expression of glycine-N-methyltransferase (Gnmt), which is the main metabolic enzyme for SAM, is significantly decreased in the WFRs, compared to non-diabetic control rats. In the present study, we found that the addition of Met with the LPD abrogates the beneficial effects induced by the LPD in diabetic kidney. A LPD could exert a renoprotective effect through the suppression of mTORC1 and restoration of autophagy, which is associated with reduced levels of SAM due to low-Met intake, in diabetic kidney.

Academic Significance and Societal Importance of the Research Achievements

臨床上,低蛋白質食は糖尿病性腎臓病を含む慢性腎臓病抑制の為の食事療法であるが,不適切な低蛋白質食は,蛋白質-エネルギバランスの不均衡やサルコペニアなどの栄養障害の危険を伴う.低メチオニン食や,メチオニン含有量が豊富な赤身肉などの動物性蛋白質の回避は,低蛋白質食の栄養障害の危険の軽減とともに低蛋白質食代替え食となる可能性がある. 低メチオニン食は,健康的な代謝の維持,心血管疾患の抑制などの利点を提供することに加えて,糖尿病性腎臓病を有する2型糖尿病患者とっての新規食事療法となり得る. しかし低メチオニン食がヒトの糖尿病性腎臓病を抑制できるかについては更なる研究が必要である.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results) Book (2 results)

  • [Journal Article] Methionine Abrogates the Renoprotective Effect of a Low-Protein Diet Against Diabetic Kidney Disease in Obese Rats With Type 2 Diabetes2020

    • Author(s)
      Kitada M, Ogura Y, Monno I, Xu J, Koya D.
    • Journal Title

      Aging (Albany NY)

      Volume: 12 Issue: 5 Pages: 4489-4505

    • DOI

      10.18632/aging.102902

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The impact of dietary protein intake on longevity and metabolic health.2019

    • Author(s)
      Kitada M, Ogura Y, Monno I, Koya D.
    • Journal Title

      EBioMedicine.

      Volume: - Pages: 632-640

    • DOI

      10.1016/j.ebiom.2019.04.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 2型糖尿病/肥満ラットにおける腎尿細管Gnmt低下とメチオニン代謝産物SAMの蓄積は糖尿病性腎臓病の病態形成に関与している2019

    • Author(s)
      北田宗弘、小倉慶雄、門野至、古家大祐
    • Organizer
      第19回日本抗加齢医学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 摂取蛋白質の“量”と“質”の観点から糖尿病性腎臓病に対する食事療法を考える2019

    • Author(s)
      北田宗弘、古家大祐
    • Organizer
      第34回日本糖尿病合併症学会シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Book] 特集 健康長寿を目指した食事療法の設定根拠とその実際 糖尿病性腎症患者の食事療法―低蛋白質食を中心に―2019

    • Author(s)
      北田宗弘
    • Total Pages
      5
    • Publisher
      内分泌・糖尿病・代謝内科
    • Related Report
      2019 Annual Research Report
  • [Book] 特集 糖尿病の食事療法を極める 蛋白質の摂取量と糖尿病の管理―糖尿病性腎症における低蛋白質食を考える―2019

    • Author(s)
      北田宗弘
    • Total Pages
      6
    • Publisher
      月刊糖尿病
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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