ArticleThe Journal of clinical investigation2015
DNA methylation directs functional maturation of pancreatic β cells.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 156 citations in OpenAlex.
- Epigenetic modifications in type 2 diabetes mellitus.Hormones (Athens, Greece) · 2026Review
- Developmental Control of DNA Damage Responses in α- and β-Cells Shapes the Selective β-Cell Susceptibility in Diabetes.Diabetes · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Mapping histologic and functional maturation of human endocrine pancreas across early postnatal periods.Nature communications · 2026Article
- Islet cell DNA methylation in human ageing and diabetes.Nature metabolism · 2026Article
- Mitochondria as Epigenetic Regulators of β-Cell Identity and Plasticity: A Metabolo-Epigenetic Perspective.Cells · 2026Review
- Reconstructing the Islets: Advances in 3D Pancreatic Organoid Models for Functional β-Cell Replacement.International journal of molecular sciences · 2026Review
- Developmental control of DNA damage responses in α- and β-cells shapes the selective beta-cell susceptibility in diabetes.bioRxiv : the preprint server for biology · 2025Article
- Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors.Nature communications · 2025Article
- FXYD2 marks and regulates maturity of β cells via ion channel-mediated signal transduction.Nature communications · 2025Article
- Epigenetic memory as crucial contributing factor in directing the differentiation of human iPSC into pancreatic β-cells in vitro.Cell and tissue research · 2025Review
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- Beta cell-specific PAK1 enrichment ameliorates diet-induced glucose intolerance in mice by promoting insulin biogenesis and minimising beta cell apoptosis.Diabetologia · 2025Article
- Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.Biochemical Society transactions · 2024Review
- Disruption of perinatal myeloid niches impacts the aging clock of pancreatic β cells.iScience · 2024Article
- High-Fat Diets Fed during Pregnancy Cause Changes to Pancreatic Tissue DNA Methylation and Protein Expression in the Offspring: A Multi-Omics Approach.International journal of molecular sciences · 2024Article
- Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity.Diabetologia · 2024Article
- CaFrontiers in endocrinology · 2024Review
- Adjudin improves beta cell maturation, hepatic glucose uptake and glucose homeostasis.Diabetologia · 2024Article
- Beta cell dedifferentiation in type 1 diabetes: sacrificing function for survival?Frontiers in endocrinology · 2024Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic β cells secrete insulin in response to postprandial increases in glucose levels to prevent hyperglycemia and inhibit insulin secretion under fasting conditions to protect against hypoglycemia. β cells lack this functional capability at birth and acquire glucose-stimulated insulin secretion (GSIS) during neonatal life. Here, we have shown that during postnatal life, the de novo DNA methyltransferase DNMT3A initiates a metabolic program by repressing key genes, thereby enabling the coupling of insulin secretion to glucose levels. In a murine model, β cell-specific deletion of Dnmt3a prevented the metabolic switch, resulting in loss of GSIS. DNMT3A bound to the promoters of the genes encoding hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) - both of which regulate the metabolic switch - and knockdown of these two key DNMT3A targets restored the GSIS response in islets from animals with β cell-specific Dnmt3a deletion. Furthermore, DNA methylation-mediated repression of glucose-secretion decoupling genes to modulate GSIS was conserved in human β cells. Together, our results reveal a role for DNA methylation to direct the acquisition of pancreatic β cell function.
Indexed as
Identifiers
What OpenQuestion holds
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.