ArticleDiabetes2023
DNA Methylation-Dependent Restriction of Tyrosine Hydroxylase Contributes to Pancreatic β-Cell Heterogeneity.
Article in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Structural and functional impact of cystic fibrosis on endocrine pancreatic innervation.Clinical science (London, England : 1979) · 2026Article
- 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
- Role of the DNA methyltransferases in diabetes mellitus and Its complications.Molecular biology reports · 2026Review
- Syntaxin 4 protects islet β-cells from cytokine-induced senescence.Frontiers in endocrinology · 2026Article
- 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
- High-resolution imaging atlas reveals the context-dependent role of pancreatic sympathetic innervation in diabetic mice.Acta biochimica et biophysica Sinica · 2025Article
- Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors.Nature communications · 2025Article
- Review
- Dopaminergic neurons in the paraventricular hypothalamus extend the food consumption phase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
- Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.Biochemical Society transactions · 2024Review
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity.Diabetologia · 2024Article
- Investigation of Pancreatic-beta Cells Role in the Biological Process of Ageing.Endocrine, metabolic & immune disorders drug targets · 2024Review
- DNA Methylation in the Hypothalamic Feeding Center and Obesity.Journal of obesity & metabolic syndrome · 2023Review
- Differential CpG methylation atbioRxiv : the preprint server for biology · 2023Article
- The pathogenic "symphony" in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas.Cell metabolism · 2023Review
- Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The molecular and functional heterogeneity of pancreatic β-cells is well recognized, but the underlying mechanisms remain unclear. Pancreatic islets harbor a subset of β-cells that co-express tyrosine hydroxylase (TH), an enzyme involved in synthesis of catecholamines that repress insulin secretion. Restriction of the TH+ β-cells within islets is essential for appropriate function in mice, such that a higher proportion of these cells corresponds to reduced insulin secretion. Here, we use these cells as a model to dissect the developmental control of β-cell heterogeneity. We define the specific molecular and metabolic characteristics of TH+ β-cells and show differences in their developmental restriction in mice and humans. We show that TH expression in β-cells is restricted by DNA methylation during β-cell differentiation. Ablation of de novo DNA methyltransferase Dnmt3a in the embryonic progenitors results in a dramatic increase in the proportion of TH+ β-cells, whereas β-cell-specific ablation of Dnmt3a does not. We demonstrate that maintenance of Th promoter methylation is essential for its continued restriction in postnatal β-cells. Loss of Th promoter methylation in response to chronic overnutrition increases the number of TH+ β-cells, corresponding to impaired β-cell function. These results reveal a regulatory role of DNA methylation in determining β-cell heterogeneity.
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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.