ArticleMolecular endocrinology (Baltimore, Md.)2012
Pax6 is crucial for β-cell function, insulin biosynthesis, and glucose-induced insulin secretion.
Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 121 citations in OpenAlex.
- The paracrine signalling between endothelial and pancreatic β-cells: implications for oxidative stress and diabetes.Journal of endocrinological investigation · 2026Review
- Esculetin induces apoptosis and functional impairment in INS-1 pancreatic β-cells associated with ER stress and MAPK/JNK signaling.Protoplasma · 2026Article
- A dish-to-biobank framework links β-cell nutrient-stress programs to genetic and dietary risk for Type 2 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines.Stem cell reports · 2026Article
- In vitro assessment of the impact of di(2-ethylhexyl) phthalate and its metabolites on the function and transcription of key glucose sensing proteins in a rat pancreatic β-cell line.BMC research notes · 2026Article
- TBL1X/TBL1XR1 govern β-cell identity through a PAX6-containing gene regulatory network.Nature communications · 2026Article
- Review
- Differential expression of POMC-processing genes in corticotroph tumors.Endocrine oncology (Bristol, England) · 2026Article
- Modeling combinatorial regulation from single-cell multi-omics provides regulatory units underpinning cell type landscape using cRegulon.Genome biology · 2025Article
- Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies.Cell communication and signaling : CCS · 2025Review
- A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets.Stem cell research & therapy · 2025Review
- PDX1 in early pregnancy is associated with decreased risks of gestational diabetes mellitus and adverse pregnancy outcomes.Frontiers in endocrinology · 2025Article
- Zebrafish: unraveling genetic complexity through duplicated genes.Development genes and evolution · 2024Review
- scParser: sparse representation learning for scalable single-cell RNA sequencing data analysis.Genome biology · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Beta-Cell Tipe1 Orchestrates Insulin Secretion and Cell Proliferation by Promoting Gαs/cAMP Signaling via USP5.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Stem Cell Therapy for the Management of Type 1 Diabetes: Advances and Perspectives.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling.International journal of biological sciences · 2024Article
- Immunometabolic alterations in type 2 diabetes mellitus revealed by single-cell RNA sequencing: insights into subtypes and therapeutic targets.Frontiers in immunology · 2024Article
- Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy.EMBO molecular medicine · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Pax6 transcription factor is crucial for endocrine cell differentiation and function. Indeed, mutations of Pax6 are associated with a diabetic phenotype and a drastic decrease of insulin-positive cell number. Our aim was to better define the β-cell Pax6 transcriptional network and thus provide further information concerning the role of Pax6 in β-cell function. We developed a Pax6-deficient model in rat primary β-cells with specific small interfering RNA leading to a 75% knockdown of Pax6 expression. Through candidate gene approach, we confirmed that Pax6 controls the mRNA levels of the insulin 1 and 2, Pdx1, MafA, GLUT2, and PC1/3 genes in β-cells. Importantly, we identified new Pax6 target genes coding for GK, Nkx6.1, cMaf, PC2, GLP-1R and GIPR which are all involved in β-cell function. Furthermore, we demonstrated that Pax6 directly binds and activates specific elements on the promoter region of these genes. We also demonstrated that Pax6 knockdown led to decreases in insulin cell content, in insulin processing, and a specific defect of glucose-induced insulin secretion as well as a significant reduction of GLP-1 action in primary β-cells. Our results strongly suggest that Pax6 is crucial for β-cells through transcriptional control of key genes coding for proteins that are involved in insulin biosynthesis and secretion as well as glucose and incretin actions on β-cells. We provide further evidence that Pax6 represents a key element of mature β-cell function.
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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.