SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared…

• NR
  National Research Foundation

  Award: NRF-2016R1A5A1010764
• YU
  Yonsei University
• MO
  Ministry of Trade, Industry and Energy

  Award: 10063335
• MO
  Ministry of Science, ICT and Future Planning

  Awards: NRF-2016R1A5A1010764, NRF-2017R1C1B5015044
• KH
  Korea Health Industry Development Institute

  Award: HI17C0913
• NR
  National Research Foundation of Korea

  Awards: 2016R1A5A1010764, NRF-2016R1A5A1010764, HI17C0913, NRF-2017R1C1B5015044
• YU
  Yonsei University College of Medicine

  Award: 6-2016-0082