Pyroptosis Plays an Essential Role in Immune Responses of Type 2 Diabetes Mellitus

Abstract

Background: Diabetes is a common immune-metabolic disease, and it has become the third non-communicable disease threatening human health and life after cardiovascular disease and tumor. Among them, type 2 diabetes is a more common condition. Inflammation is closely related to the pathogenesis and complications of diabetes. Type 2 diabetes-related risk factors such as inflammation and high glucose have been shown to induce pyroptosis, but it is still unclear whether pyroptosis is involved in the pathogenesis of type 2 diabetes. Methods: This study aimed to explore whether pyroptosis is involved in the pathogenesis of type 2 diabetes by bioinformatics analysis of transcriptomic data of tissue samples from patients with type 2 diabetes and healthy control samples from the GEOs dataset. Results: Differential gene expression analysis showed that five pyroptosis-related genes, NLRP3, ELANE, IL-6, SCAF11 and CASP1, were differentially expressed in patients with type 2 diabetes. Cluster analysis found that there were two types of pyrop-tosis in diabetic patients. PCA and pathway enrichment analysis revealed different gene expression profiles in the two patterns. The CIBERSORT algorithm assessed immune cell composition and found that patients with different patterns exhibited different immune cell infiltrations. The network analysis results of key genes showed that the above five pyroptosis-related genes have targeted miRNAs and transcription factors, except for the SCAF11 gene. The SCAFII gene has no predicted target drugs in the DGIdb database, but the other four genes have targeted drugs. Conclusions: Our results suggest that pyroptosis is involved in the pathogenesis of type 2 diabetes and may regulate the immune response in type 2 diabetes.