ArticleMolecular metabolism2017
Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05166447 (Twenty-year Follow-up of the Inter99 Cohort), which is not on this map. Cited by 51 papers, 3 of them syntheses that pooled it.
What it found
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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.
Twenty-year Follow-up of the Inter99 Cohort
Who cites it
51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Exploring the genomic and transcriptomic profiles of glycemic traits and drug repurposing.Journal of biomedical science · 2025Pooled it
- Unlocking the power of empagliflozin: Rescuing inflammation in hyperglycaemia-exposed human cardiomyocytes through comprehensive multi-level analysis.European journal of heart failure · 2025Pooled it
- Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.Human genetics · 2023Pooled it
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- Emerging Role of Transcription Factor 19 (TCF19) in Inflammatory Disease and Cancer.Biomolecules · 2026Review
- A bioinformatics screen identifies TCF19 as an aggressiveness-sustaining gene in prostate cancer.Molecular oncology · 2025Article
- Downregulation of TCF19 and ATAD2 causes endothelial cell cycle arrest at the transition from cardiac hypertrophy to heart failure.Basic research in cardiology · 2025Article
- Gene expression changes in pancreatic α-cell lines following knock-out Of either CK2α or CK2α'.Biological research · 2025Article
- The upregulation of GDF15 is controlled epigenetically by oncogenic TCF19 signaling in human hepatocellular carcinoma.iScience · 2025Article
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Genome-wide associations with metabolic syndrome among UK Biobank participants reporting use of second-generation antipsychotics.Pharmacotherapy · 2025Article
- Activators of the 26S proteasome when protein degradation increases.Experimental & molecular medicine · 2025Review
- Article
- Genomic variations associated with risk and protection against vincristine-induced peripheral neuropathy in pediatric cancer patients.NPJ genomic medicine · 2024Article
- Functional genetics reveals the contribution of delta opioid receptor to type 2 diabetes and beta-cell function.Nature communications · 2024Article
- Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes.Nature communications · 2023Article
- Analysis of D-amino acids secreted from murine islets of Langerhans using Marfey's reagent and reversed phase LC-MS/MS.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2023Article
- Identification of novel hypermethylated or hypomethylated CpG sites and genes associated with anthracycline-induced cardiomyopathy.Scientific reports · 2023Article
- Associations of genetic markers of diabetes mellitus with carotid atherosclerosis: a community-based case-control study.Cardiovascular diabetology · 2023Article
- Monogenic diabetes.Nature reviews. Disease primers · 2023Review
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
objectivesGenome-wide association studies (GWAS) have identified >100 loci independently contributing to type 2 diabetes (T2D) risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells.
methodsThe expression of 104 candidate T2D susceptibility genes was measured in a human multi-tissue panel, through PCR-free expression assay. The effects of the knockdown of beta-cell enriched genes were next investigated on insulin secretion from the human EndoC-βH1 beta-cell line. Finally, we performed RNA-sequencing (RNA-seq) so as to assess the pathways affected by the knockdown of the new genes impacting insulin secretion from EndoC-βH1, and we analyzed the expression of the new genes in mouse models with altered pancreatic beta-cell function.
resultsWe found that the candidate T2D susceptibility genes' expression is significantly enriched in pancreatic beta cells obtained by laser capture microdissection or sorted by flow cytometry and in EndoC-βH1 cells, but not in insulin sensitive tissues. Furthermore, the knockdown of seven T2D-susceptibility genes (
conclusionsThis study showed the ability of post-GWAS functional studies to identify new genes and pathways involved in human pancreatic beta-cell function and in T2D pathophysiology.
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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.