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The effect of indirect energy restriction due to glucose excretion by SGLT2 inhibitor on life longevity and aging

Research Project

Project/Area Number 21K08540
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionKawasaki Medical School

Principal Investigator

OBATA Atsushi  川崎医科大学, 医学部, 特任研究員 (10771298)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsSGLT2阻害薬 / 健康寿命 / 寿命延長 / 間接的カロリー制限 / 加齢現象
Outline of Research at the Start

現在、糖尿病治療薬の一つとしてSGLT2阻害薬が実臨床で多くの患者さんに利用されている。SGLT2阻害薬は尿糖排泄を促進することで、体重増加抑制効果、血糖改善効果を有する。一方で、様々な動物種で経口的なカロリー制限が寿命延長に寄与すると報告されている。本研究では、経口的なカロリー制限ではなく、SGLT2阻害薬による尿糖排泄という「間接的カロリー制限」が寿命及び加齢現象に及ぼす影響を明らかにすることを主旨としている。また、若年期からSGLT2阻害薬を投与することで寿命・老化現象に及ぼす影響に加えて、中・壮年期からSGLT2阻害薬を投与することで寿命・老化現象に及ぼす影響に差がないかを検討する。

Outline of Final Research Achievements

It has been reported that caloric restriction retards aging and extend life span in various species.Therefore, we examined whether SGLT2 inhibitors could show favorable effects on longevity.SGLT2 inhibitors have not only glucose-lowering effects but also favorable effects on physical strength, oxidative stress, telomere length and longevity. We think that SGLT2 inhibitor-mediated calorie loss, reduction of oxidative stress, and extension of telomere length contributes to extension of life span.

Academic Significance and Societal Importance of the Research Achievements

SGLT2阻害薬は現在抗糖尿病薬としてだけでなく、心不全患者や慢性腎臓病にも適応となっている。様々な動物種でカロリー制限が寿命延長効果を有することが知られており、我々は同量のカロリー摂取状態の際に、SGLT2阻害薬を使用することで尿糖排泄に伴う間接的なカロリーロスが健康寿命に与える影響を検討した。その結果、SGLT2阻害薬は握力や走行可能距離を延長し、寿命延長効果があることを明らかにした。SGLT2阻害薬は長期投与により、摂取カロリーがそろっている範疇においては健康寿命が延長することが明らかとなった。SGLT2阻害薬が健康寿命を延長する可能性を示唆する非常に社会的意義を有する研究成果と言える。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 2021

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 10 results)

  • [Journal Article] Efficacy and safety of pemafibrate in patients with hypertriglyceridemia in clinical settings: A retrospective study.2023

    • Author(s)
      Katakura Y, Shimoda M, Ohnishi M, Kusano T, Dan K, Isobe H, Wamata R, Iwamoto Y, Fushimi Y, Sanada J, Obata A, Kimura T, Tatsumi F, Nakanishi S, Mune T, Kaku K, Kaneto H.
    • Journal Title

      Nutr Metab Cardiovasc Dis.

      Volume: 7 Issue: 7 Pages: 1444-1452

    • DOI

      10.1016/j.numecd.2023.02.011

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive Search for GPCR Compounds which Can Enhance MafA and/or PDX-1 Expression Levels Using a Small Molecule Compound Library.2023

    • Author(s)
      Kaneto H, Obata A, Shimoda M, Kimura T, Obata Y, Ikeda T, Moriuchi S, Nakanishi S, Mune T, Kaku K.
    • Journal Title

      J Diabetes Res.

      Volume: 8 Pages: 1-8

    • DOI

      10.1155/2023/8803172

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules.2022

    • Author(s)
      Sanada J, Obata A, Fushimi Y, Kimura T, Shimoda M, Ikeda T, Nogami Y, Obata Y, Yamasaki Y, Nakanishi S, Mune T, Kaku K, Kaneto H.
    • Journal Title

      Sci Rep.

      Volume: 12 Issue: 1 Pages: 13220-13220

    • DOI

      10.1038/s41598-022-17657-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus. Biomedicines.2022

    • Author(s)
      Kaneto H, Kimura T, Shimoda M, Obata A, Sanada J, Fushimi Y, Matsuoka TA, Kaku K.
    • Journal Title

      Biomedicines.

      Volume: 31 Issue: 4 Pages: 818-831

    • DOI

      10.3390/biomedicines10040818

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Switching From Daily DPP-4 Inhibitor to Once-Weekly GLP-1 Receptor Activator Dulaglutide Significantly Ameliorates Glycemic Control in Subjects With Poorly Controlled Type 2 Diabetes Mellitus: A Retrospective Observational Study.2022

    • Author(s)
      Sanada J, Kimura T, Shimoda M, Tomita A, Fushimi Y, Kinoshita T, Obata A, Okauchi S, Hirukawa H, Kohara K, Tatsumi F, Nakanishi S, Mune T, Kaku K, Kaneto H.
    • Journal Title

      Front Endocrinol (Lausanne)

      Volume: 6

    • DOI

      10.3389/fendo.2021.714447

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Favorable effects of GLP-1 receptor activator against pancreatic beta-cell glucose toxicity and the development of arteriosclerosis: “The earlier, the better” in therapy with incretin-based medicine.2021

    • Author(s)
      Kaneto H, Kimura T, Shimoda M, Obata A, Sanada J, Fushimi Y, Nakanishi S, Mune T, and Kaku K.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 22 Issue: 15 Pages: 7917-7917

    • DOI

      10.3390/ijms22157917

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History2021

    • Author(s)
      Kaneto H, Kimura T, Obata A, Shimoda M, Kaku K.
    • Journal Title

      Int J Mol Sci .

      Volume: 22 Issue: 5 Pages: 2596-2596

    • DOI

      10.3390/ijms22052596

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class2021

    • Author(s)
      Kaneto H, Obata A, Kimura T, Shimoda M, Kinoshita T, Matsuoka TA, Kaku K.
    • Journal Title

      Int J Mol Sci .

      Volume: 22 Issue: 6 Pages: 3062-3062

    • DOI

      10.3390/ijms22063062

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice.2021

    • Author(s)
      Fushimi Y, Obata A, Sanada J, Nogami Y, Ikeda T, Yamasaki Y, Obata Y, Shimoda M, Nakanishi S, Mune T, Kaku K, Kaneto H.
    • Journal Title

      Sci Rep.

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-94896-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dulaglutide exerts beneficial anti atherosclerotic effects in ApoE knockout mice with diabetes: the earlier, the better2021

    • Author(s)
      Sanada J, Obata A, Obata Y, Fushimi Y, Shimoda M, Kohara K, Nakanishi S, Mune T, Kaku K, Kaneto H.
    • Journal Title

      Sci Rep .

      Volume: 11 Issue: 1 Pages: 1425-1425

    • DOI

      10.1038/s41598-020-80894-x

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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