ArticleThe Journal of clinical investigation2023
Nutrient regulation of the islet epigenome controls adaptive insulin secretion.
Article in The Journal of clinical investigation, 2023. 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, 23 citations in OpenAlex.
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Workload-induced changes to cell state contribute to β-cell failure in diabetes.bioRxiv : the preprint server for biology · 2026Article
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- c-Jun regulates postpartum β-cell apoptosis and survival downstream of prolactin signaling.Molecular and cellular endocrinology · 2025Article
- Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors.Nature communications · 2025Article
- Heterogeneous enhancer states orchestrate β cell responses to metabolic stress.Nature communications · 2024Article
- Loss of glucose-stimulated β-cell Nr4a1 expression impairs insulin secretion and glucose homeostasis.American journal of physiology. Cell physiology · 2024Article
- Single-housing-induced islet epigenomic changes are related to polymorphisms in diabetic KK mice.Life science alliance · 2024Article
- Lysine acetyltransferase 14 mediates TGF-β-induced fibrosis in ovarian endometrioma via co-operation with serum response factor.Journal of translational medicine · 2024Article
- Glucose metabolism partially regulates β-cell function through epigenomic changes.Journal of diabetes investigation · 2024Review
- A role and mechanism for redox sensing by SENP1 in β-cell responses to high fat feeding.Nature communications · 2024Article
- Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding.Cell death & disease · 2023Article
- Understanding cell fate acquisition in stem-cell-derived pancreatic islets using single-cell multiome-inferred regulomes.Developmental cell · 2023Article
- Peeling the onion: another layer in the regulation of insulin secretion.The Journal of clinical investigation · 2023Article
- Article
- It's What and When You Eat: An Overview of Transcriptional and Epigenetic Responses to Dietary Perturbations in Pancreatic Islets.Frontiers in endocrinology · 2022Review
- Pan-AMPK activator O304 prevents gene expression changes and remobilisation of histone marks in islets of diet-induced obese mice.Scientific reports · 2021Article
- Transcriptional mechanisms of pancreatic β-cell maturation and functional adaptation.Trends in endocrinology and metabolism: TEM · 2021Review
- Understanding Dietary Intervention-Mediated Epigenetic Modifications in Metabolic Diseases.Frontiers in genetics · 2020Review
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Adaptation of the islet β cell insulin-secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in β cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurred at sites occupied by the chromatin-modifying enzyme lysine-specific demethylase 1 (Lsd1) in islets. β Cell-specific deletion of Lsd1 led to insulin hypersecretion, aberrant expression of nutrient-response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited shared epigenetic and transcriptional changes. Moreover, we found that genetic variants associated with type 2 diabetes were enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined and clinically relevant. Overall, these studies revealed that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome.
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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.