ArticleThe Journal of clinical investigation2023
Type 2 diabetes candidate genes, including PAX5, cause impaired insulin secretion in human pancreatic islets.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 50 citations in OpenAlex.
- AS160 Overexpression Protects Against β-Cell Failure in Hyperglycemic Mice by Interacting With HSPA8 to Regulate Mitophagy.Acta physiologica (Oxford, England) · 2026Article
- Proteomic analysis of pancreatic endocrine cells by mechanistic single-cell isolation identifies membrane pathways.Experimental & molecular medicine · 2026Article
- Adipocyte Expression of O-Glycoprotein Procollagen C-Endopeptidase Enhancer Protein 2 (PCPE2): Mechanisms Linking Fibrosis and Beiging of White Adipose Tissue.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic landscapes in human pancreatic islets reveal distinct drivers for adaptation to age and type 2 diabetes.Nature communications · 2026Article
- PCPE1 and PCPE2: When Sequence Similarity Masks Functional Diversity.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- Article
- Nanopore Electroporation: A New Delivery Method Within the Field of Epigenetic Editing.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes.Nature metabolism · 2026Article
- RNA-seq at different stages of human pancreatic β cell differentiation reveals proliferation dynamics and SMAD9 in directing β cell fate.Cell death & disease · 2026Article
- Review
- Network-based insights into miRNA regulation of β-cell insulin secretion in type 2 diabetes.iScience · 2025Article
- Identification of circulating miRNA alterations in diabetes patients excluding periodontitis effects: insights into target gene downregulation in diabetic complications.Annals of medicine · 2025Article
- From Human to Mouse and Back Again: Genetic and Genomic Ta(i)les of Islet Dysfunction in Type 2 Diabetes.Annual review of genetics · 2025Review
- Single-cell mRNA-regulation analysis reveals cell type-specific mechanisms of type 2 diabetes.Nature communications · 2025Article
- Evaluating cell-specific gene expression using single-cell and single-nuclei RNA-sequencing data from human pancreatic islets of the same donors.Scientific reports · 2025Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- The role of the beta cell in type 2 diabetes: new findings from the last 5 years.Diabetologia · 2025Review
- Molecular correlates of glycine receptor activity in human β cells.Molecular metabolism · 2025Article
- Bioinformatics-led identification of pathophysiological hallmark genes in diabesotension via graph clustering method.Journal of diabetes and metabolic disorders · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
27 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes (T2D) is caused by insufficient insulin secretion from pancreatic β cells. To identify candidate genes contributing to T2D pathophysiology, we studied human pancreatic islets from approximately 300 individuals. We found 395 differentially expressed genes (DEGs) in islets from individuals with T2D, including, to our knowledge, novel (OPRD1, PAX5, TET1) and previously identified (CHL1, GLRA1, IAPP) candidates. A third of the identified expression changes in islets may predispose to diabetes, as expression of these genes associated with HbA1c in individuals not previously diagnosed with T2D. Most DEGs were expressed in human β cells, based on single-cell RNA-Seq data. Additionally, DEGs displayed alterations in open chromatin and associated with T2D SNPs. Mouse KO strains demonstrated that the identified T2D-associated candidate genes regulate glucose homeostasis and body composition in vivo. Functional validation showed that mimicking T2D-associated changes for OPRD1, PAX5, and SLC2A2 impaired insulin secretion. Impairments in Pax5-overexpressing β cells were due to severe mitochondrial dysfunction. Finally, we discovered PAX5 as a potential transcriptional regulator of many T2D-associated DEGs in human islets. Overall, we have identified molecular alterations in human pancreatic islets that contribute to β cell dysfunction in T2D pathophysiology.
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