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Title: 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.

Authors: Marques, Emily Sara; Formato, Emily; Liang, Wenle; Leonard, Emily; Timme-Laragy, Alicia R

Published In J Diabetes, (2022 Jan)

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 α- and β-cells. METHODS: Annotated sc-RNA-Seq data from six studies of human pancreatic islets from metabolically healthy and donors with T2DM were collected. α- and 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: α- and β-cells from T2DM donors modified genes involved in energy metabolism, immune response, autophagy, and cellular stress. α- and 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.

PubMed ID: 34725923 Exiting the NIEHS site

MeSH Terms: Diabetes Mellitus, Type 2*/genetics; Diabetes Mellitus, Type 2*/metabolism; Humans; Insulin-Secreting Cells*/metabolism; Oxidation-Reduction; Pancreas/metabolism; Transcriptome

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