ArticleDiabetologia2016
Methylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
- Trained immunity: New insights into pathogenesis and therapeutic targets in diabetes and diabetic complications.Genes & diseases · 2026Review
- Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026Review
- Tet2 modulates ER stress responses related to β-cell death and autoimmunity in diabetes.iScience · 2026Article
- Type 1 diabetes mellitus induced by sintilimab: a case report and related case literature analysis.Frontiers in endocrinology · 2026Review
- Epigenetics in evolution and adaptation to environmental challenges: pathways for disease prevention and treatment.Epigenomics · 2025Review
- Epigenetic Alterations in Alzheimer's Disease: Impact on Insulin Signaling and Advanced Drug Delivery Systems.Biology · 2024Review
- Integrated DNA Methylation and Transcriptomics Analyses of Lacrimal Glands Identify the Potential Genes Implicated in the Development of Sjögren's Syndrome-Related Dry Eye.Journal of inflammation research · 2023Article
- RyR2/IRBIT regulates insulin gene transcript, insulin content, and secretion in the insulinoma cell line INS-1.Scientific reports · 2022Article
- Epigenetic modifications in pancreas development, diabetes, and therapeutics.Medicinal research reviews · 2022Review
- The Prospective Application of Melatonin in Treating Epigenetic Dysfunctional Diseases.Frontiers in pharmacology · 2022Review
- Diabetes: discovery of insulin, genetic, epigenetic and viral infection mediated regulation.The Nucleus : an international journal of cytology and allied topics · 2022Review
- Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes.Nature communications · 2021Article
- Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?).Nature reviews. Endocrinology · 2021Review
- Insights Into the Role of DNA Methylation in Immune Cell Development and Autoimmune Disease.Frontiers in cell and developmental biology · 2021Review
- Revisiting the Antigen-Presenting Function of β Cells in T1D Pathogenesis.Frontiers in immunology · 2021Review
- DNA Methylation Patterning and the Regulation of Beta Cell Homeostasis.Frontiers in endocrinology · 2021Review
- High-fat diet-induced and genetically inherited obesity differentially alters DNA methylation profile in the germline of adult male rats.Clinical epigenetics · 2020Article
- Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes.Biomedical reports · 2020Article
- Clinical value of DNA methylation markers in autoimmune rheumatic diseases.Nature reviews. Rheumatology · 2020Review
- Tumor Necrosis Factor α Influences Phenotypic Plasticity and Promotes Epigenetic Changes in Human Basal Forebrain Cholinergic Neuroblasts.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisType 1 diabetes is caused by the immunological destruction of pancreatic beta cells. Preclinical and clinical data indicate that there are changes in beta cell function at different stages of the disease, but the fate of beta cells has not been closely studied. We studied how immune factors affect the function and epigenetics of beta cells during disease progression and identified possible triggers of these changes.
methodsWe studied FACS sorted beta cells and infiltrating lymphocytes from NOD mouse and human islets. Gene expression was measured by quantitative real-time RT-PCR (qRT-PCR) and methylation of the insulin genes was investigated by high-throughput and Sanger sequencing. To understand the role of DNA methyltransferases, Dnmt3a was knocked down with small interfering RNA (siRNA). The effects of cytokines on methylation and expression of the insulin gene were studied in humans and mice.
resultsDuring disease progression in NOD mice, there was an inverse relationship between the proportion of infiltrating lymphocytes and the beta cell mass. In beta cells, methylation marks in the Ins1 and Ins2 genes changed over time. Insulin gene expression appears to be most closely regulated by the methylation of Ins1 exon 2 and Ins2 exon 1. Cytokine transcription increased with age in NOD mice, and these cytokines could induce methylation marks in the insulin DNA by inducing methyltransferases. Similar changes were induced by cytokines in human beta cells in vitro. CONCLUSIONS/
interpretationEpigenetic modification of DNA by methylation in response to immunological stressors may be a mechanism that affects insulin gene expression during the progression of type 1 diabetes.
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