ArticleDiabetologia2020
Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 66 citations in OpenAlex.
- Epigenetic modifications in type 2 diabetes mellitus.Hormones (Athens, Greece) · 2026Review
- BMI-dependent methylation and clinical signatures in North Indian women with PCOS.The Indian journal of medical research · 2026Article
- Morphostructural Analysis of PAH-Rich Human Adipose Tissue: A Potential Silent Sequestration Site.International journal of molecular sciences · 2026Article
- Epigenetic regulation in a high-sugar environment (Review).International journal of molecular medicine · 2026Review
- A Novel mechanism for depot-specific leptin gene expression regulation and its persistence after weight loss.iScience · 2026Article
- Systematic investigation of interindividual variation of DNA methylation in human whole blood.Genome biology · 2026Article
- Review
- The beneficial effect of hepatic ER stress-associated protein PDI on obesity-associated glucose dysregulation.Nutrition & metabolism · 2025Article
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- NPB-1575 attenuates neuroinflammation and resists ferroptosis in rat ischemic stroke via IRS2 signaling pathway.Acta pharmacologica Sinica · 2025Article
- IRS2/FOXO1 mitigates osteoarthritis by regulating chondrocyte autophagy and mitochondrial function.Molecular medicine (Cambridge, Mass.) · 2025Article
- Article
- Functionally characterizing obesity-susceptibility genes using CRISPR/Cas9, in vivo imaging and deep learning.Scientific reports · 2025Article
- Exploring the role of insulin resistance in bridging the metabolic syndrome and Alzheimer's disease-a review of mechanistic studies.Frontiers in endocrinology · 2025Review
- Assessment of Changes in the Expression of Genes Involved in Insulin Signaling and Glucose Transport in Leukocytes of Women with Gestational Diabetes During Pregnancy and in the Postpartum Period.International journal of molecular sciences · 2024Article
- Article
- Article
- Epigenetic Alterations in Alzheimer's Disease: Impact on Insulin Signaling and Advanced Drug Delivery Systems.Biology · 2024Review
- Epigenetic modifications in obesity-associated diseases.MedComm · 2024Review
- Crosstalk between MIR-96 and IRS/PI3K/AKT/VEGF cascade in hRPE cells; A potential target for preventing diabetic retinopathy.PloS one · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIRS2 is an important molecular switch that mediates insulin signalling in the liver. IRS2 dysregulation is responsible for the phenomenon of selective insulin resistance that is observed in type 2 diabetes. We hypothesise that epigenetic mechanisms are involved in the regulation of IRS2 in the liver of obese and type 2 diabetic individuals.
methodsDNA methylation of seven CpG sites was studied by bisulphite pyrosequencing and mRNA and microRNA (miRNA) expression was assessed by quantitative real-time PCR in liver biopsies of 50 obese non-diabetic and 31 obese type 2 diabetic participants, in a cross-sectional setting. Methylation-sensitive luciferase assays and electrophoretic mobility shift assays were performed. Furthermore, HepG2 cells were treated with insulin and high glucose concentrations to induce miRNA expression and IRS2 downregulation.
resultsWe found a significant downregulation of IRS2 expression in the liver of obese individuals with type 2 diabetes (0.84 ± 0.08-fold change; p = 0.0833; adjusted p value [p CONCLUSIONS/
interpretationOur study highlights a new multi-layered epigenetic network that could be involved in subtle dysregulation of IRS2 in the liver of individuals with type 2 diabetes. This might lead to fine-tuning of IRS2 expression and is likely to be supplementary to the already known factors regulating IRS2 expression. Thereby, our findings could support the discovery of new diagnostic and therapeutic strategies for type 2 diabetes. Graphical abstract.
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