ArticlePLoS genetics2014
Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 3 of them syntheses 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
279 citing papers in PubMed, 3 syntheses or guidelines pooled it, 503 citations in OpenAlex.
- DNA methylation and type 2 diabetes: a systematic review.Clinical epigenetics · 2024Pooled it
- Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells.Frontiers in cell and developmental biology · 2020Pooled it
- Pooled it
- A nomogram for predicting 5-year incidence of type 2 diabetes in a Chinese population.Endocrine · 2020Trial
- MASLD, diabetes and PMOS across the female life stages.Diabetologia · 2026Review
- The Bidirectional Relationship Between Diabetes and Cancer: Mechanistic Insights, Epigenetic Intermediaries, and Therapeutic Approaches.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Review
- Impact of Genetics on Endocrine Manifestations of Cystic Fibrosis.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2026Review
- DNA methylation-mediated suppression of endocytosis confers resistance to duck hepatitis A virus type 3.Microbiology spectrum · 2026Article
- The Impact of Maternal Obesity and Diabetes on the Development of Congenital Heart Defects (CHDs) in Offspring: A Narrative Review.Metabolites · 2026Review
- Nanopore Electroporation: A New Delivery Method Within the Field of Epigenetic Editing.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- H19 inhibition orchestrates DNMT3B-dependent epigenetic reprogramming of glycolytic enzymes in the liver during diabetes.Cell communication and signaling : CCS · 2026Article
- Early blood DNA methylation patterns associated with glycemic progression in a prospective Indian cohort.Clinical epigenetics · 2026Article
- Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes.Nature metabolism · 2026Article
- Islet cell DNA methylation in human ageing and diabetes.Nature metabolism · 2026Article
- Epigenetic adaptation of beta cells across lifespan and disease.Nature metabolism · 2026Article
- The Future of Epigenetics: Emerging Technologies and Clinical Applications.ACS pharmacology & translational science · 2026Review
- Diet intervention altered DNA methylation of potassium voltage-gated channel subfamily Q member 1 in metabolic dysfunction-associated steatohepatitis.Clinical epigenetics · 2026Article
- Molecular mechanisms and structure-activity relationships of natural polysaccharides in ameliorating type 2 diabetes mellitus: a comprehensive review.Frontiers in nutrition · 2026Review
- Network-based insights into miRNA regulation of β-cell insulin secretion in type 2 diabetes.iScience · 2025Article
- DNA methylation markers of insulin resistance surrogate measures in the Atherosclerosis Risk in Communities (ARIC) study.Epigenetics · 2025Article
219 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired insulin secretion is a hallmark of type 2 diabetes (T2D). Epigenetics may affect disease susceptibility. To describe the human methylome in pancreatic islets and determine the epigenetic basis of T2D, we analyzed DNA methylation of 479,927 CpG sites and the transcriptome in pancreatic islets from T2D and non-diabetic donors. We provide a detailed map of the global DNA methylation pattern in human islets, β- and α-cells. Genomic regions close to the transcription start site showed low degrees of methylation and regions further away from the transcription start site such as the gene body, 3'UTR and intergenic regions showed a higher degree of methylation. While CpG islands were hypomethylated, the surrounding 2 kb shores showed an intermediate degree of methylation, whereas regions further away (shelves and open sea) were hypermethylated in human islets, β- and α-cells. We identified 1,649 CpG sites and 853 genes, including TCF7L2, FTO and KCNQ1, with differential DNA methylation in T2D islets after correction for multiple testing. The majority of the differentially methylated CpG sites had an intermediate degree of methylation and were underrepresented in CpG islands (∼ 7%) and overrepresented in the open sea (∼ 60%). 102 of the differentially methylated genes, including CDKN1A, PDE7B, SEPT9 and EXOC3L2, were differentially expressed in T2D islets. Methylation of CDKN1A and PDE7B promoters in vitro suppressed their transcriptional activity. Functional analyses demonstrated that identified candidate genes affect pancreatic β- and α-cells as Exoc3l silencing reduced exocytosis and overexpression of Cdkn1a, Pde7b and Sept9 perturbed insulin and glucagon secretion in clonal β- and α-cells, respectively. Together, our data can serve as a reference methylome in human islets. We provide new target genes with altered DNA methylation and expression in human T2D islets that contribute to perturbed insulin and glucagon secretion. These results highlight the importance of epigenetics in the pathogenesis of 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.