Effect of SGLT2 inhibitor on cardioprotective effect

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11086
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Nagasaki University
• Principal Investigator: ICHINOMIYA Taiga 長崎大学, 医歯薬学総合研究科(医学系), 助教 (50404249)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 薬理学的プレコンディショニング / 心筋虚血再灌流傷害 / SGLT2阻害薬

Outline of Final Research Achievements

SGLT1 inhibition of SGLT2 inhibitor may abrogate the effect of internal cardioprotection. This study was performed to investigate the effect of tofogliflozin, clinical drug of SGLT2 inhibitor, against ischemic reperfusion injury, and to develop the pharmacological cardioprotection even under SGLT1 inhibition.
SGLT1 inhibition abrogated the internal cardioprotective effect, and AMPK played an important role in the abrogation. Additionally, the pharmacological cardioprotection which is independent of AMPK signaling had the protective effect even under SGLT1 inhibition. Furthermore, tofogliflozin which is high selectivity of SGLT2 inhibition doesn't abrogate the internal cardioprotection.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

SGLT2阻害薬は糖尿病の重大な合併症である心血管イベント発生を抑制することを示した最新の治療薬である。しかし、SGLT2阻害薬が持つSGLT1阻害作用は心筋虚血再灌流傷害での内在性臓器保護を抑制する可能性が示唆され、また、SGLT2阻害薬の効果が不十分な患者に対するSGLT1/2阻害薬の開発も進められている。本研究の結果から、SGLT1阻害作用はやはり内在性臓器保護を抑制するものの、SGLT2選択性の高いSGLT2阻害薬であれば虚血再灌流傷害での内在性心筋保護効果を抑制しないことが示された。また、AMPKを介さない薬理学的心筋保護法であればSGLT1阻害下でも効果を得ることが明らかとなった。