ArticleDiabetologia2008
Hypermethylation of hepatic Gck promoter in ageing rats contributes to diabetogenic potential.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 86 citations in OpenAlex.
- Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.Nature medicine · 2022Trial
- Evaluation for CpG island methylation of FASN and SREBP promoter in Mongolian gerbil NAFLD model.Archives of medical science : AMS · 2025Article
- Epigenetic Alterations in Alzheimer's Disease: Impact on Insulin Signaling and Advanced Drug Delivery Systems.Biology · 2024Review
- Glucokinase and glucokinase activator.Life metabolism · 2023Review
- A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity.Nature communications · 2023Article
- Emerging trends in DNA and RNA methylation modifications in type 2 diabetes mellitus: a bibliometric and visual analysis from 1992 to 2022.Frontiers in endocrinology · 2023Article
- Construction of PIK3C3 Transgenic Pig and Its Pathogenesis of Liver Damage.Life (Basel, Switzerland) · 2022Article
- Neonatal Vitamin C and Cysteine Deficiencies Program Adult Hepatic Glutathione and Specific Activities of Glucokinase, Phosphofructokinase, and Acetyl-CoA Carboxylase in Guinea Pigs' Livers.Antioxidants (Basel, Switzerland) · 2021Article
- Research Progress on Epigenetics of Diabetic Cardiomyopathy in Type 2 Diabetes.Frontiers in cell and developmental biology · 2021Review
- The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy.Disease markers · 2021Article
- The Effects of Dietary Interventions on DNA Methylation: Implications for Obesity Management.International journal of molecular sciences · 2020Review
- Developmental programming: Prenatal testosterone-induced changes in epigenetic modulators and gene expression in metabolic tissues of female sheep.Molecular and cellular endocrinology · 2020Article
- How Dietary Factors Affect DNA Methylation: Lesson from Epidemiological Studies.Medicina (Kaunas, Lithuania) · 2020Review
- The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus.Clinical epigenetics · 2020Review
- Dietary Leucine Supplementation Restores Serum Glucose Levels, and Modifying Hepatic Gene Expression Related to the Insulin Signal Pathway in IUGR Piglets.Animals : an open access journal from MDPI · 2019Article
- Hallmarks of Aging in the Liver.Computational and structural biotechnology journal · 2019Review
- DNA methylation landscapes in the pathogenesis of type 2 diabetes mellitus.Nutrition & metabolism · 2018Review
- Epigenetic mechanisms underlying the link between non-alcoholic fatty liver diseases and nutrition.Nutrients · 2014Review
- Article
- GCK gene-body hypomethylation is associated with the risk of coronary heart disease.BioMed research international · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisHepatic glucokinase (GCK) is a key enzyme in glucose utilisation. Downregulation of its activity is associated with insulin resistance and type 2 diabetes mellitus. However, it is unknown whether hepatic Gck expression is influenced by age and is involved in ageing-mediated diabetes, and whether the degree of methylation of the hepatic Gck promoter is correlated with the transcription of Gck. To address the question, we evaluated hepatic Gck transcription and promoter methylation in young (14 weeks), adult (40 weeks) and aged (80 weeks) rats.
methodsHepatic glycogen, Gck expression and the kinase activity of GCK were measured in three age groups. The CpG methylation status was determined by both bisulphite direct sequencing and clone sequencing of the PCR amplificates of Gck promoter. The causal relationship between Gck methylation and mRNA expression was confirmed by treating rat primary hepatocytes with 5-aza-2'-deoxycytidine (5-Aza-CdR).
resultsWe have shown an age-associated decline in hepatic glycogen, Gck expression levels and the kinase activity of hepatic GCK. The eleven CpG sites studied displayed age-related progressive methylation changes in hepatic Gck promoter, which were confirmed by two methods: direct and clone sequencing. After 5-Aza-CdR treatment of rat primary hepatocytes, there was a fourfold increase in Gck expression. CONCLUSIONS/
interpretationOur results demonstrate that an age-related increase in methylation is negatively associated with hepatic Gck expression, suggesting that DNA methylation could be involved in increasing age-dependent susceptibility to hepatic insulin resistance and diabetes. Thus, the epigenetic modification of the hepatic Gck promoter may represent an important marker for diabetogenic potential during the ageing process.
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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.