ArticleNature communications2023
PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed, 34 citations in OpenAlex.
- ProtectiveiScience · 2026Article
- Cataract GWAS meta-analysis and multi-omics Mendelian randomisation inform disease mechanisms and candidate target prioritisation.EBioMedicine · 2026Article
- A functional missense variant iniScience · 2026Article
- Charting Endocrine Progenitors Across Species and Organs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets.Nature communications · 2026Article
- Functional Inactivation ofInternational journal of molecular sciences · 2026Article
- Epigenetic regulation in type II diabetes: linking molecular mechanisms to clinical management.Journal of diabetes and metabolic disorders · 2026Review
- PAX4 R192H variant impairs β cell function by disrupting β cell identity and compensatory capacity in response to metabolic stress.Genome medicine · 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
- STARD10 regulates human pancreatic β cell differentiation and triglyceride metabolism.Stem cell reports · 2026Article
- Review
- Article
- dentification and characterization of novelBMJ open diabetes research & care · 2025Article
- Obesity-Driven Metabolic Disorders: The Interplay of Inflammation and Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Diabetes mellitus polygenic risk scores: heterogeneity and clinical translation.Nature reviews. Endocrinology · 2025Review
- Article
- Phenotypic and Genetic Diversity in Diabetes Across Populations.The Journal of clinical endocrinology and metabolism · 2025Review
- Young-onset type 2 diabetes-Epidemiology, pathophysiology, and management.Journal of diabetes investigation · 2025Review
- RFX3 is essential for the generation of functional human pancreatic islets from stem cells.Diabetologia · 2025Article
- PAX Family, Master Regulator in Cancer.Diagnostics (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
Abstract
The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell development and/or function is unknown. Participants carrying the PAX4 p.His192 allele exhibited decreased pancreatic beta cell function compared to homozygotes for the p.192Arg allele in a cross-sectional study in which we carried out an intravenous glucose tolerance test and an oral glucose tolerance test. In a pedigree of a patient with young onset diabetes, several members carry a newly identified p.Tyr186X allele. In the human beta cell model, EndoC-βH1, PAX4 knockdown led to impaired insulin secretion, reduced total insulin content, and altered hormone gene expression. Deletion of PAX4 in human induced pluripotent stem cell (hiPSC)-derived islet-like cells resulted in derepression of alpha cell gene expression. In vitro differentiation of hiPSCs carrying PAX4 p.His192 and p.X186 risk alleles exhibited increased polyhormonal endocrine cell formation and reduced insulin content that can be reversed with gene correction. Together, we demonstrate the role of PAX4 in human endocrine cell development, beta cell function, and its contribution to T2D-risk.
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Registered trials
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.