ArticleThe Journal of clinical investigation2004
Foxa2 regulates multiple pathways of insulin secretion.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Cross-ancestry analysis of gestational diabetes mellitus identifies novel loci, drug targets and biological pathways.Frontiers in endocrinology · 2026Pooled it
- Article
- FOXA2 in islet biology: Orchestrating pancreatic development and glucose homeostasis.Genes & diseases · 2026Review
- Modeling combinatorial regulation from single-cell multi-omics provides regulatory units underpinning cell type landscape using cRegulon.Genome biology · 2025Article
- FOXM1 cooperates with ERα to regulate functional β-cell mass.American journal of physiology. Endocrinology and metabolism · 2025Article
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- An Insight into Vital Genes Responsible for β-cell Formation.Advances in experimental medicine and biology · 2024Article
- Feeding during hibernation shifts gene expression toward active season levels in brown bears (Physiological genomics · 2023Article
- Syndromic forms of congenital hyperinsulinism.Frontiers in endocrinology · 2023Review
- DNA Sequence and Structure under the Prism of Group Theory and Algebraic Surfaces.International journal of molecular sciences · 2022Article
- Article
- TAZ promotes PDX1-mediated insulinogenesis.Cellular and molecular life sciences : CMLS · 2022Article
- Evidence That Substantia Nigra Pars Compacta Dopaminergic Neurons Are Selectively Vulnerable to Oxidative Stress Because They Are Highly Metabolically Active.Frontiers in cellular neuroscience · 2022Review
- Sulfonylurea Receptor 1 in Central Nervous System Injury: An Updated Review.International journal of molecular sciences · 2021Review
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity.Cell death & disease · 2021Article
- SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells.Genes & development · 2021Article
- Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis.iScience · 2021Article
- Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency.Cell death & disease · 2021Article
- Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity.Frontiers in immunology · 2021Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells. Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. We utilized expression profiling to identify additional targets of Foxa2. Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion.
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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.