Omarigliptin ameliorated high glucose-induced nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation through activating adenosine monophosphate-activated protein kinase α (AMPKα) in renal glomerular endothelial cells

• Main Authors: Ling Li, Kelei Qian, Yuli Sun, Yong Zhao, Yun Zhou, Ying Xue, Xinyu Hong
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Bioengineered
• Subjects: omarigliptin; ampk; nlrp3 inflammasome; diabetic nephropathy
• Online Access: http://dx.doi.org/10.1080/21655979.2021.1957748
• ISSN: 2165-5979; 2165-5987

Diabetic nephropathy (DN) is a complication of diabetes that induces the development of end-stage renal disease (ESRD). The pathogenesis of DN is reported to be closely related to the activation of the NOD-like receptor 3 (NLRP3) inflammasome in renal glomerular endothelial cells. Omarigliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the management of type II diabetes, it has been recently reported to possess a significant anti-inflammatory property. This study aims to explore the potential therapeutic effects of Omarigliptin on DN. We established an in vitro injury model in human renal glomerular endothelial cells (HrGECs) using high glucose (HG). The severe cytotoxicity and increased oxidative stress in HrGECs induced by HG were pronouncedly reversed by the introduction of Omarigliptin. Furthermore, the activated NLRP3 inflammasome and the excessive production of interleukin 18 (IL-18) and interleukin 1β (IL-1β) in HrGECs induced by incubation with HG were pronouncedly reversed by the introduction of Omarigliptin, accompanied by the activation of the AMPK/mTOR signaling pathway. After the co-administration of the adenosine monophosphate-activated protein kinase α (AMPKα) inhibitor, compound C, the protective effects of Omarigliptin against HG-induced NLRP3 inflammasome activation and production of pro-inflammatory factors were dramatically abolished. Taken together, our data revealed that Omarigliptin ameliorated HG-induced inflammation in renal glomerular endothelial cells through suppressing NLRP3 inflammasome activation mediated by AMPKα.