The ubiquitin‐proteasome system, which is one of the systems for cell protein homeostasis and degradation, happens through the ordered and coordinated action of three types of enzymes, E1 ubiquitin‐activating enzyme, E2 ubiquitin‐carrier enzyme, E3 ubiquitin‐protein ligase. Tripartite motif‐containing (TRIM) family proteins are the richest subfamily of really interesting new gene E3 ubiquitin ligases, which play a critical role not only in many biological processes, including proliferation, apoptosis, pyroptosis, innate immunity, and autophagy, but also many diseases like cancer, diabetes mellitus, and neurodegenerative disease. Increasing evidence suggests that TRIM family proteins play a vital role in modulating autophagy, pyroptosis, and diabetes mellitus. The aim of this review is to discuss the role of TRIM proteins in the regulation of autophagy, pyroptosis, diabetes mellitus, and diabetic complications.

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Type 2 diabetes mellitus (T2DM) is a growing worldwide epidemic and is characterized by progressive pancreatic β-cell dysfunction and insulin resistance. Tripartite motif protein 32 (TRIM32) belongs to the TRIM family protein and has been shown to be involve in insulin resistance in skeletal muscle and the liver. However, the effect of TRIM32 on pancreatic β-cell dysfunction and its mechanism remains unknown. In the current study, we found that serum TRIM32 concentrations of T2DM in patients were significantly elevated compared to those in healthy controls, which indicated that TRIM32 might be used as a diagnostic biomarker in T2DM patients. In INS-1 cells, exposure to high glucose (HG) conditions caused a significant elevation in TRIM32 expression and TRIM32 was located in the nucleus. Overexpression of TRIM32 in INS-1 cells exacerbated the effects of HG-induced autophagy and impaired insulin secretion. In contrast, the silencing of TRIM32 produced the opposite effect. Furthermore, TRIM32 overexpression decreased the phosphorylation levels of Akt and mTOR under HG conditions. However, the activation of Akt/mTOR by MHY1485 reversed the effects of TRIM32 on HG-treated INS-1 cells. Collectively, the present results suggested that TRIM32 participates in the development of T2DM by modulating autophagic cell death and insulin secretion, which might occur through the Akt/mTOR pathway. Thus, TRIM32 might be a promising target in T2DM therapy.

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.