Background: Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance and failure of β-cells to meet the metabolic demand for insulin. Recent advances in single-cell RNA sequencing (sc-RNA-Seq) have allowed for in-depth studies to further understand the underlying cellular mechanisms of T2DM. In β-cells, redox signaling is critical for insulin production. A meta-analysis of human pancreas islet sc-RNA-Seq data was conducted to evaluate how T2DM may modify the transcriptomes of αand β-cells.Methods: Annotated sc-RNA-Seq data from six studies of human pancreatic islets from metabolically healthy and donors with T2DM were collected. αand β-cells, subpopulations of proliferating α-cells, immature, and senescent β-cells were identified based on expression levels of key marker genes. Each dataset was analyzed individually before combining, using weighted comparisons. Pathways of significant genes and individual redox-related gene expression were then evaluated to further understand the role that redox signaling may play in T2DM-induced β-cell dysfunction.Results: αand β-cells from T2DM donors modified genes involved in energy metabolism, immune response, autophagy, and cellular stress. αand β-cells also had an increased nuclear factor erythroid 2-related factor 2 (NFE2L2)mediated antioxidant response in T2DM donors. The proportion of immature and senescent β-cells increased in T2DM donors, and in immature and senescent β-cells, genes regulated by NFE2L2 were further upregulated. Conclusions: These findings suggest that NFE2L2 plays a role in β-cell maturation and dysfunction. Redox singling maybe a key pathway for β-cell restoration and T2DM therapeutics.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.