ArticleThe Journal of clinical investigation2008
Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 289 papers, 1 of them a synthesis that pooled it.
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Who cites it
289 citing papers in PubMed, 1 synthesis or guideline pooled it, 633 citations in OpenAlex.
- Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes.Nature communications · 2016Pooled it
- The role of epigenetic signatures in type 2 diabetes: therapeutic advances and lifestyle interventions.Acta diabetologica · 2026Review
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- The Impact of Maternal Obesity and Diabetes on the Development of Congenital Heart Defects (CHDs) in Offspring: A Narrative Review.Metabolites · 2026Review
- Epigenetic regulation in a high-sugar environment (Review).International journal of molecular medicine · 2026Review
- Two Sides of a Coin: Molecular, metabolic, and Phenotypic Convergence in Pediatric Undernutrition and Obesity.Current obesity reports · 2026Review
- Hyperglycemia during the first 1000 days as a driver of metabolic programming.Frontiers in endocrinology · 2026Review
- Placental mTOR signalling links mitochondrial dysfunction, nutrient transport and neonatal beta cell perturbations in mice.Diabetologia · 2025Article
- An update on current type 2 diabetes mellitus (T2DM) druggable targets and drugs targeting them.Molecular diversity · 2025Review
- Phenotype of insulin-dependent diabetes in chronic undernutrition: beta cell stress and immune dysfunction-a rural sub-Saharan perspective on type 5 diabetes.Diabetologia · 2025Review
- Potential Impact of Parental Origin of Inheritance on the Clinical Presentation of Familial Partial Lipodystrophy Type 2 Syndrome.Clinical endocrinology · 2025Article
- Epigenetic memory as crucial contributing factor in directing the differentiation of human iPSC into pancreatic β-cells in vitro.Cell and tissue research · 2025Review
- Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia.Endocrinology and metabolism (Seoul, Korea) · 2025Review
- Fetal Growth Restriction and Its Metabolism-Related Long-Term Outcomes-Underlying Mechanisms and Clinical Implications.Nutrients · 2025Review
- Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs.Scientific reports · 2024Article
- Maternal birth weight as an indicator of early and late gestational diabetes mellitus: The Japan Environment and Children's Study.Journal of diabetes investigation · 2024Article
- Rosa canina extract relieves methylation alterations of pancreatic genes in STZ-induced diabetic rats : Gene methylation in diabetic rats treated with an extract.Molecular biology reports · 2024Article
- Maternal Vitamin D Deficiency Impairs the Development of β Cells in Offspring Rats in a Sex-Dependent Manner.International journal of molecular sciences · 2024Article
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- Review
229 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Intrauterine growth retardation (IUGR) has been linked to the onset of diseases in adulthood, including type 2 diabetes, and has been proposed to result from altered gene regulation patterns due to epigenetic modifications of developmental genes. To determine whether epigenetic modifications may play a role in the development of adult diabetes following IUGR, we used a rodent model of IUGR that expresses lower levels of Pdx1, a pancreatic and duodenal homeobox 1 transcription factor critical for beta cell function and development, which develops diabetes in adulthood. We found that expression of Pdx1 was permanently reduced in IUGR beta cells and underwent epigenetic modifications throughout development. The fetal IUGR state was characterized by loss of USF-1 binding at the proximal promoter of Pdx1, recruitment of the histone deacetylase 1 (HDAC1) and the corepressor Sin3A, and deacetylation of histones H3 and H4. Following birth, histone 3 lysine 4 (H3K4) was demethylated and histone 3 lysine 9 (H3K9) was methylated. During the neonatal period, these epigenetic changes and the reduction in Pdx1 expression could be reversed by HDAC inhibition. After the onset of diabetes in adulthood, the CpG island in the proximal promoter was methylated, resulting in permanent silencing of the Pdx1 locus. These results provide insight into the development of type 2 diabetes following IUGR and we believe they are the first to describe the ontogeny of chromatin remodeling in vivo from the fetus to the onset of disease in adulthood.
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