ArticleLaboratory investigation; a journal of technical methods and pathology2018
Interleukin-6 determines protein stabilization of DNA methyltransferases and alters DNA promoter methylation of genes associated with insulin signaling and angiogenesis.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Epigenome-wide association study of circulating interleukin-6 connects DNA methylation to immunometabolic and inflammatory health.Communications biology · 2026Pooled it
- Humanized Antibodies Targeting Ectodomains of IL-6R and GP130 Suppress IL-6/STAT3 Signalling and Tumour Growth in Breast Cancer Models.Journal of cellular and molecular medicine · 2026Article
- From molecular damage to regulatory constraint: epigenetic and metabolic limits of cellular plasticity in aging.Frontiers in aging · 2026Review
- A comprehensive review on the implications of Yogic/Sattvic diet in reducing inflammation in type 2 diabetes.Nutrition & diabetes · 2025Review
- Mechanism of non-coding RNA regulation of DNMT3A.Epigenetics & chromatin · 2025Article
- Article
- DNA methylation-based telomere length is more strongly associated with cardiovascular disease and long-term mortality than quantitative polymerase chain reaction-based telomere length: evidence from the NHANES 1999-2002.Clinical epigenetics · 2024Article
- Comorbidity Genes of Alzheimer's Disease and Type 2 Diabetes Associated with Memory and Cognitive Function.International journal of molecular sciences · 2024Review
- Nerve Growth Factor and the Role of Inflammation in Tumor Development.Current issues in molecular biology · 2024Review
- Rodent Models for ASD Biomarker Development.Advances in neurobiology · 2024Review
- DNA methylation and histone post-translational modifications in atherosclerosis and a novel perspective for epigenetic therapy.Cell communication and signaling : CCS · 2023Review
- DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response.European journal of ophthalmology · 2023Article
- Epigenetic marks associated with gestational diabetes mellitus across two time points during pregnancy.Clinical epigenetics · 2023Article
- A Rare Olive Compound Oleacein Improves Lipid and Glucose Metabolism, and Inflammatory Functions: A Comprehensive Whole-Genome Transcriptomics Analysis in Adipocytes Differentiated from Healthy and Diabetic Adipose Stem Cells.International journal of molecular sciences · 2023Article
- Clonal hematopoiesis and bone marrow inflammation.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Epigenetics and stroke: role of DNA methylation and effect of aging on blood-brain barrier recovery.Fluids and barriers of the CNS · 2023Article
- Epigenetics and stroke: role of DNA methylation and effect of aging on blood-brain barrier recovery.Research square · 2023Article
- Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions.Journal of translational medicine · 2022Article
- Epigenetic perspectives of COVID-19: Virus infection to disease progression and therapeutic control.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Article
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 at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Individuals with type 2 diabetes (T2D) display vascular insulin resistance and decreased nitric oxide production leading to vasoconstriction and atherosclerosis. Soluble factors such as pro-inflammatory molecules, and various genetic and epigenetic mechanisms have been implicated to induce insulin resistance in vascular endothelial cells. Epigenetic mechanisms such as altered promoter DNA methylation have been demonstrated in development and progression of metabolic disorders and atherosclerosis. However, underlying precise epigenetic mechanisms regulating cross talk between insulin signaling genes and inflammation in vascular cells remains to be fully understood. Human endothelial cells when (a) treated with interleukin-6 (IL-6) and insulin together, (b) pretreated with IL-6, and (c) under hyperinsulinemic conditions led to a state of vascular insulin resistance resulting in decreased Akt/eNOS activation and subsequent stabilization of STAT3 phosphorylation. IL-6 abrogated insulin effects on angiogenesis in 3D spheroid and matrigel assays. IL-6-induced insulin resistance was associated with decreased activity of DNA methyltransferase isoforms and global DNA hypomethylation, which inversely correlated with S-phase of cell cycle. CpG microarray analysis in IL-6 treated endothelial cells revealed promoters associated hypo- and hypermethylation of 199 and 98 genes respectively. Promoter DNA methylation status of genes associated with insulin signaling and angiogenesis such as RPS6KA2, PIK3R2, FOXD3, EXOC7, MAP3K8, ITPKB, EPHA6, IGF1R, and FOXC2 were validated by bisulfite DNA sequencing. Concentration and time-dependent analysis revealed that IL-6 reduced DNMT1 and DNMT3B but not DNMT3A protein levels. Our data indicate a causal link between IL-6-induced changes in global and promoter-specific DNA methylation, due to reduced DNMT1 and DNMT3B protein levels leading to altered expression of critical genes involved in insulin signaling and angiogenesis.
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.