| Project/Area Number |
17H06767
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Research Collaborator |
Tomita Issei
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 糖尿病性腎症 / ケトン体 / mTORC1 / 動脈硬化 / 糖尿病性腎臓病 |
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| Outline of Final Research Achievements |
The aim of this study was to verify our hypothesis that plasma ketone body levels increased by SGLT2 inhibitor should be involved in its renoprotective action against atherosclerosis-related kidney injury. Treatement with either an SGLT2 inhibitor or 1,3-butandiol (a ketone body precusor) ameliorated kidney inury in atherosclerosis mouse model. The renoprotective effect of SGLT2 was canceled in mice lacking Hmgcs2, a rate-limiting enzyme for endogenous ketogenesis. Furthremore, mTORC1 inhibition was involved in the mechanism behind ketone body-mediated renoprotection. Collectively, ketone body increase is involved in SGLT2 inhibitors-mediated renoprotection. Energy supply with ketone body into kidneys and subsequent mTORC1 inhibition may be a novel therapeutic target for atherosclerogenic kidney injury in diabetes.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、腎症における現在未解決の課題に対して、基礎研究からのアプローチにより、現行の治療では難治性の腎症に対する新規治療標的の探索を目指したものである。現在、腎症からの透析導入数は横ばいになろうとしているが、今後、糖尿病患者の爆発的増加が起こることも予想されている。現在の治療に甘んじることは、現時点で治療指針を示せていない難治性腎症からの透析導入数の増加を招く可能性を残すことになる。よって本研究により、腎症におけるmTORC1過剰亢進の意義、そして、その抑制機構としてのケトン体の可能性が示されたことは、今後の腎症予後改善に大きな貢献をもたらすことが期待される。
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