ArticleScientific reports2015
PAX4 Defines an Expandable β-Cell Subpopulation in the Adult Pancreatic Islet.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 58 citations in OpenAlex.
- Functional Inactivation ofInternational journal of molecular sciences · 2026Article
- PAX4 R192H variant impairs β cell function by disrupting β cell identity and compensatory capacity in response to metabolic stress.Genome medicine · 2026Article
- dentification and characterization of novelBMJ open diabetes research & care · 2025Article
- Comparative β-cell development: insights from Rodents, humans and induced pluripotent stem cell models.Stem cell research & therapy · 2025Review
- Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.eLife · 2025Article
- Pax4 in Health and Diabetes.International journal of molecular sciences · 2023Review
- Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses.Frontiers in cell and developmental biology · 2023Article
- NR5A2/LRH-1 regulates the PTGS2-PGEiScience · 2022Article
- Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes?International journal of molecular sciences · 2021Review
- Establishment of a long-term stable β-cell line and its application to analyze the effect of Gcg expression on insulin secretion.Scientific reports · 2021Article
- Article
- Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus.International journal of molecular sciences · 2019Review
- Dissecting the Brain/Islet Axis in Metabesity.Genes · 2019Review
- LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.Nature communications · 2018Article
- The type 2 diabetes-associated HMG20A gene is mandatory for islet beta cell functional maturity.Cell death & disease · 2018Article
- Alpha TC1 and Beta-TC-6 genomic profiling uncovers both shared and distinct transcriptional regulatory features with their primary islet counterparts.Scientific reports · 2017Article
- Review
- Replicative capacity of β-cells and type 1 diabetes.Journal of autoimmunity · 2016Review
- Pax4 Gene Delivery Improves Islet Transplantation Efficacy by Promoting β Cell Survival and α-to-β Cell Transdifferentiation.Cell transplantationArticle
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PAX4 is a key regulator of pancreatic islet development whilst in adult acute overexpression protects β-cells against stress-induced apoptosis and stimulates proliferation. Nonetheless, sustained PAX4 expression promotes β-cell dedifferentiation and hyperglycemia, mimicking β-cell failure in diabetic patients. Herein, we study mechanisms that allow stringent PAX4 regulation endowing favorable β-cell adaptation in response to changing environment without loss of identity. To this end, PAX4 expression was monitored using a mouse bearing the enhanced green fluorescent protein (GFP) and cre recombinase construct under the control of the islet specific pax4 promoter. GFP was detected in 30% of islet cells predominantly composed of PAX4-enriched β-cells that responded to glucose-induced insulin secretion. Lineage tracing demonstrated that all islet cells were derived from PAX4(+) progenitor cells but that GFP expression was confined to a subpopulation at birth which declined with age correlating with reduced replication. However, this GFP(+) subpopulation expanded during pregnancy, a state of active β-cell replication. Accordingly, enhanced proliferation was exclusively detected in GFP(+) cells consistent with cell cycle genes being stimulated in PAX4-overexpressing islets. Under stress conditions, GFP(+) cells were more resistant to apoptosis than their GFP(-) counterparts. Our data suggest PAX4 defines an expandable β-cell sub population within adult islets.
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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.