ArticleThe Journal of clinical investigation2017
PAX6 maintains β cell identity by repressing genes of alternative islet cell types.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 157 citations in OpenAlex.
- Predictive control of human pancreatic cell fate using a digital model ofbioRxiv : the preprint server for biology · 2026Article
- Gene expression profiles associated with stimulus-responsive insulin secretion in insulinoma.Endocrine connections · 2026Article
- TBL1X/TBL1XR1 govern β-cell identity through a PAX6-containing gene regulatory network.Nature communications · 2026Article
- Single-cell RNA-seq and in vitro study reveal Fusobacterium nucleatum impairs β-cell identity in type 2 diabetes via the NF-κB-CDKN1C axis.Journal of translational medicine · 2026Article
- Review
- Gc inhibition preserves insulin sensitivity and reduces body weight without loss of muscle mass.JCI insight · 2025Article
- Single-cell mRNA-regulation analysis reveals cell type-specific mechanisms of type 2 diabetes.Nature communications · 2025Article
- Review
- Trapα deficiency impairs the early events of insulin biosynthesis and glucose homeostasis.The Journal of clinical investigation · 2025Article
- NKX2.2 and KLF4 cooperate to regulate α-cell identity.Genes & development · 2025Article
- Roles for the long non-coding RNAiScience · 2025Article
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- Hormone-switching islet cells: parallels to transmitter-switching neurons.Frontiers in cell and developmental biology · 2025Article
- Recent advances in pancreatic α-cell transdifferentiation for diabetes therapy.Frontiers in immunology · 2025Review
- Exploring the key role of DNA methylation as an epigenetic modulator in oxidative stress related islet cell injury in patients with type 2 diabetes mellitus: a review.Journal of diabetes and metabolic disorders · 2024Review
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Article
- Review
- Repression of latent NF-κB enhancers by PDX1 regulates β cell functional heterogeneity.Cell metabolism · 2024Article
- Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes.Cell metabolism · 2024Article
30 more citing papers are in PubMed but not listed here.
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12 authors at 2 institutions in 1 country.
Funding
Abstract
Type 2 diabetes is thought to involve a compromised β cell differentiation state, but the mechanisms underlying this dysfunction remain unclear. Here, we report a key role for the TF PAX6 in the maintenance of adult β cell identity and function. PAX6 was downregulated in β cells of diabetic db/db mice and in WT mice treated with an insulin receptor antagonist, revealing metabolic control of expression. Deletion of Pax6 in β cells of adult mice led to lethal hyperglycemia and ketosis that were attributed to loss of β cell function and expansion of α cells. Lineage-tracing, transcriptome, and chromatin analyses showed that PAX6 is a direct activator of β cell genes, thus maintaining mature β cell function and identity. In parallel, we found that PAX6 binds promoters and enhancers to repress alternative islet cell genes including ghrelin, glucagon, and somatostatin. Chromatin analysis and shRNA-mediated gene suppression experiments indicated a similar function of PAX6 in human β cells. We conclude that reduced expression of PAX6 in metabolically stressed β cells may contribute to β cell failure and α cell dysfunction in diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.