Role of Ketone body metabolism in diabetic kidney disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08241
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Kume Shinji 滋賀医科大学, 医学部, 助教 (00452235)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 糖尿病性腎臓病 / ケトン体 / mTORC1

Outline of Final Research Achievements

SGLT2 inhibitors, an important class of anti-diabetes drugs, have been found to offer potent protection from kidney disease, a critical comorbidity of diabetes. But how they offer such protection has not been clear. The present study showed that SGLT2 inhibitors promote the elevation of ketone bodies by enhancing ketogenesis. The ketone bodies, in turn, were shown to act on kidney cells where they inhibit the excess activation of an important energy-sensing intracellular pathway, allowing better function of the organ. Such an effect could be replicated by exogenous supplementation with ketone bodies, even in non-diabetic mouse models of kidney disease. Thus, these findings have broad implications for the potential treatment of kidney pathologies.

Free Research Field

糖尿病性腎臓病

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎臓病は我が国の透析導入原疾患一位の疾患であり、新たな治療法の開発が望まれている。本研究により、これまで、糖尿病急性合併症ケトアシドーシスの原因物質としてネガティブなイメージが根付いていたケトン体に、糖尿病による臓器障害を予防しうる秘めたる力が存在するという、糖尿病におけるケトン体の位置づけにパラ ダイムシフトを起こす結果が導き出された。そしてその効果が、近年類を見ない腎予後改善効果を発揮している新規糖尿病治療薬 SGLT2阻害薬の腎臓保護効果の一端を担っていることも明らかとなった。今回明らかとされたケトン体の持つ臓器保護効果に、今後の糖尿病性腎臓病克服への期待がもたれる。