Tripartite motif protein 32 overexpression promotes inflammation and pyroptosis in INS-1 cells via the NF-κB/NLRP3 signaling pathway under high glucose conditions

Abstract Background: Type 2 diabetes mellitus (T2DM) is an inflammatory disease, and the primary features are insulin resistance and β-cell dysfunction. Inflammation and pyroptosis contribute to insulin resistance and β-cell dysfunction. Therefore, it is important to identify novel biomarkers to alleviate inflammation and pyroptosis in T2DM. Tripartite motif protein 32 (TRIM32) belongs to the TRIM family and is involved in inflammation, oxidative stress, apoptosis, and autophagy. Moreover, TRIM32 participates in insulin resistance in skeletal muscle and liver; however, its role in β-cell dysfunction remains elusive. Herein, this study investigated the role of TRIM32 in inflammation and pyroptosis in INS-1 cells.Methods and Results: This study confirmed for the first time that serum TRIM32 was upregulated in T2DM patients by ELISA, and high glucose-induced TRIM32 expression in INS-1 cells was validated by western blot, quantitative real-time reverse transcriptase-polymerase chain reaction, and immunofluorescence staining. Overexpression of TRIM32 promoted inflammation and pyroptosis in INS-1 cells under high glucose conditions, whereas silencing TRIM32 had the opposite effects. TUNEL staining and lactate dehydrogenase release assays were performed. In addition, BAY 11-7082 blocked the NF-κB/NLRP3 signaling pathway and significantly attenuated INS-1 cells inflammation and pyroptosis in a high glucose environment. Conclusions: Overexpression of TRIM32 promoted inflammation and pyroptosis in INS-1 cells partly through the NF-κB/NLRP3 signaling pathway under high glucose conditions.