ArticleOncotarget2016
Inhibition of DNA methyltransferase 1 increases nuclear receptor subfamily 4 group A member 1 expression and decreases blood glucose in type 2 diabetes.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- DNA methylation and type 2 diabetes: a systematic review.Clinical epigenetics · 2024Pooled it
- Skeletal muscle Nur77 and NOR1 insulin responsiveness is blunted in obesity and type 2 diabetes but improved after exercise training.Physiological reports · 2019Trial
- Bioinformatics analysis identifies key secretory protein-encoding differentially expressed genes in adipose tissue of metabolic syndrome.Adipocyte · 2025Article
- Investigation methylation status of tumor suppressor geneMolecular biology research communications · 2025Article
- Nuclear receptors in ovarian cancer: changing paradigms in cancer therapeutics.Frontiers in oncology · 2024Review
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
- Epigenetics in Obesity and Diabetes Mellitus: New Insights.Nutrients · 2023Review
- Diabetic Hearts Exhibit Global DNA Hypermethylation That Alter the Mitochondrial Functional Genes to Enhance the Sensitivity of the Heart to Ischemia Reperfusion Injury.Biomedicines · 2022Article
- Epigenetics: key to improve delayed wound healing in type 2 diabetes.Molecular and cellular biochemistry · 2022Review
- SARS-CoV-2 Interaction with Human DNA Methyl Transferase 1: A Potential Risk for Increasing the Incidence of Later Chronic Diseases in the Survived Patients.International journal of preventive medicine · 2022Article
- Nuclear Receptors in Energy Metabolism.Advances in experimental medicine and biology · 2022Article
- The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus.Clinical epigenetics · 2020Review
- Targeting Orphan Nuclear Receptors NR4As for Energy Homeostasis and Diabetes.Frontiers in pharmacology · 2020Review
- Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes.PloS one · 2020Article
- Antizyme inhibitor 1 genetic polymorphisms associated with diabetic patients validated in the livers of diabetic mice.Experimental and therapeutic medicine · 2019Article
- Diet-induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity.Food science & nutrition · 2019Review
- Hematopoietically expressed homeobox gene is associated with type 2 diabetes in KK Cg-AExperimental and therapeutic medicine · 2018Article
- DNA methylation, through DNMT1, has an essential role in the development of gastrointestinal smooth muscle cells and disease.Cell death & disease · 2018Article
- DNA methylation landscapes in the pathogenesis of type 2 diabetes mellitus.Nutrition & metabolism · 2018Review
- The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Metabolic Diseases.Journal of diabetes research · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous genome-wide association studies showed that DNA methyltransferase 1 (DNMT1) is associated with increased susceptibility to type 2 diabetes (T2D) in Han Chinese individuals. Here, we aimed to further evaluate the role of DNMT1 in T2D. We performed a genome-wide DNA methylation array and found that the nuclear receptor subfamily 4 group A member 1 (NR4A1) promoter was hypermethylated in patients with T2D and in a mouse model of T2D. Moreover, DNA hypermethylation of the NR4A1 promoter reduced NR4A1 mRNA expression. Transient transfection of human NR4A1 into RIN-m5F and 293T cells caused DNMT1 inhibition and induced insulin receptor activation. NR4A1knockdown by shRNA resulted in overexpression of DNMT1 and inhibition of insulin receptor, suggesting that the NR4A1 gene is involved in the epigenetics pathway. Furthermore, T2D model mice treated with the DNMT1 inhibitor aurintricarboxylic acid (ATA) showed reduced activation of DNMT1 in pancreatic β cells; this effect reversed the changes in NR4A1 expression and decreased blood glucose in T2D model mice. Thus, our results showed for the first time that DNMT1 caused NR4A1 DNA hypermethylation and blocked insulin signaling in patients with T2D. Importantly, ATA therapy may be useful for decreasing blood glucose levels by reversing NR4A1-dependent insulin signaling. These findings improve our understanding of the crucial roles of these regulatory elements in human T2D.
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.