Immunometabolic disorders in type 2 diabetes mellitus mediated by NLRP3 inflammasome activation and methods of pharmacological correction thereof

According to recent studies, chronic systemic inflammation mediated by activation of the inflammasome NOD-like receptor protein 3 (NLRP3) is a key factor in the pathophysiology of type 2 diabetes mellitus (DM). The main features of the activation of signalling cascades and regulatory mechanisms of the NLRP3 inflammasome in type 2 DM are related to the fact that glucose, saturated fatty acids, lipotoxic ceramides, oxidised LDL and cholesterol act as the main molecular patterns associated with damage, activating the inflammasome and triggering a cascade of signalling mechanisms leading to the production of IL-1β and pro-inflammatory cytokines. A number of antidiabetic drugs not only effectively control glucose levels, but also correct immunometabolic disorders associated with NLRP3 inflammasome activation. Given the role of interleukin-1β (IL-1β) in the inflammation associated with type 2 DM, anti-IL-1 therapies such as anakinra, canakinumab and gevokizumab are being investigated in both experimental models of DM and clinical trials. However, the use of this group is limited by the increased risk of infection. Among the inhibitors of NLRP3 inflammasome activation, MCC950, OLT1177, CY-09 are the most studied, but none of the compounds in this group are currently used in clinical practice. The aim of this review is to assess the role of the NLRP3 inflammasome in the pathogenesis of type 2 diabetes, as well as the potential of inflammasome pathway inhibitors as promising therapeutic agents.

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