ArticleDiabetologia2016
Transcription factor Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in rodent models.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review.Frontiers in endocrinology · 2021Pooled it
- Role of the E26 transformation specific transcription factor family in metabolic disorders.Journal of endocrinological investigation · 2025Review
- Nickel Sulfate-Induced GSIS Injury in MIN6 Cells by Activating the JNK Pathway Through Oxidative Stress.Biological trace element research · 2025Article
- Gain of pancreatic beta cell-specific SCD1 improves glucose homeostasis by maintaining functional beta cell mass under metabolic stress.Diabetologia · 2025Article
- Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Angiotensin (1-7) Improves Pancreatic Islet Function via Upregulating PDX-1 and GCK: A Dose-Dependent Study in Mice.International journal of endocrinology · 2024Article
- NR3C1/Glucocorticoid receptor activation promotes pancreatic β-cell autophagy overload in response to glucolipotoxicity.Autophagy · 2023Article
- Vertical transmission of the gut microbiota influences glucose metabolism in offspring of mice with hyperglycaemia in pregnancy.Microbiome · 2022Article
- Influence of circulating nesfatin-1, GSH and SOD on insulin secretion in the development of T2DM.Frontiers in public health · 2022Article
- Article
- E26 transformation-specific 1 is implicated in the inhibition of osteogenic differentiation induced by chronic high glucose by directly regulating Runx2 expression.Journal of biomedical research · 2021Article
- M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3β/β-catenin pathway in mice.Diabetologia · 2021Article
- Article
- Systems Approach to Pathogenic Mechanism of Type 2 Diabetes and Drug Discovery Design Based on Deep Learning and Drug Design Specifications.International journal of molecular sciences · 2020Article
- Inhibition of heparanase protects against pancreatic beta cell death in streptozotocin-induced diabetic mice via reducing intra-islet inflammatory cell infiltration.British journal of pharmacology · 2020Article
- Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes.Molecular biology reports · 2020Article
- Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats.Cells · 2020Article
- Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation.Diabetologia · 2020Article
- Heterozygous deletion of Seipin in islet beta cells of male mice has an impact on insulin synthesis and secretion through reduced PPARγ expression.Diabetologia · 2020Article
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 3 institutions in 2 countries.
Funding
Abstract
aims/hypothesis'Glucotoxicity' is a term used to convey the negative effect of hyperglycaemia on beta cell function; however, the underlying molecular mechanisms that impair insulin secretion and gene expression are poorly defined. Our objective was to define the role of transcription factor v-ets avian erythroblastosis virus E26 oncogene homologue 1 (Ets-1) in beta cell glucotoxicity.
methodsPrimary islets and Min6 cells were exposed to high glucose and Ets-1 expression was measured. Recombinant adenovirus and transgenic mice were used to upregulate Ets-1 expression in beta cells in vitro and in vivo, and insulin secretion was assessed. The binding activity of H3/H4 histone on the Ets-1 promoter, and that of forkhead box (FOX)A2, FOXO1 and Ets-1 on the Pdx-1 promoter was measured by chromatin immunoprecipitation and quantitative real-time PCR assay.
resultsHigh glucose induced upregulation of Ets-1 expression and hyperacetylation of histone H3 and H4 at the Ets-1 gene promoter in beta cells. Ets-1 overexpression dramatically suppressed insulin secretion and biosynthesis both in vivo and in vitro. Besides, Ets-1 overexpression increased the activity of FOXO1 but decreased that of FOXA2 binding to the pancreatic and duodenal homeobox 1 (PDX-1) homology region 2 (PH2), resulting in inhibition of Pdx-1 promoter activity and downregulation of PDX-1 expression and activity. In addition, high glucose promoted the interaction of Ets-1 and FOXO1, and the activity of Ets-1 binding to the Pdx-1 promoter. Importantly, PDX-1 overexpression reversed the defect in pancreatic beta cells induced by Ets-1 excess, while knockdown of Ets-1 prevented hyperglycaemia-induced dysfunction of pancreatic beta cells. CONCLUSIONS/
interpretationOur observations suggest that Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in type 2 diabetes.
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.