Relationships between type 2 diabetes, cell dysfunction, and redox signaling: A meta‐analysis of single‐cell gene expression of human pancreatic α‐ and β‐cells

Abstract

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.

Host insulin resistance caused by Porphyromonas gingivalis-review of recent progresses

“…In hepatocytes, P. gingivalis can stimulate the production of free fatty acids(FFAs). Several studies have shown that FFAs can synergize with LPS to enhance the inflammatory response.TLR2 is an important receptor for macrophage recognition of P. gingivalis and mediates the destructive chronic inflammatory response( Nishimura et al., 2015 ; Marques et al., 2022 ). It was found that TLR2 can be activated by palmitate, a free fatty acid (FFA), leading to inflammation and induction of insulin resistance ( Palmer et al., 2012 ; Furusho et al., 2013 ).…”

Recent Progress in the Diagnosis and Management of Type 2 Diabetes Mellitus in the Era of COVID-19 and Single Cell Multi-Omics Technologies

“…By applying scATAC-seq and deep learning approaches, Rai et al found that T2DM-associated SNPs were significantly enriched in beta cell-specific and common islet-specific open chromatin but not in alpha or delta cell-specific open chromatin signatures [ 179 ]. Marques et al performed a meta-analysis of the scRNA-seq data of human α- and β-cells of T2DM patients and identified disease-associated genes responsible for energy metabolism, immune homeostasis, autophagy, and especially nuclear factor erythroid 2-related factor 2 (NFE2L2) in β-cell maturation and dysfunction [ 180 ].…”