ArticleHuman molecular genetics2014
TCF7L2 is a master regulator of insulin production and processing.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 4 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.
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Who cites it
96 citing papers in PubMed, 4 syntheses or guidelines pooled it, 227 citations in OpenAlex.
- Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting.Nature genetics · 2026Pooled it
- Association of TCF7L2 genetic variants rs12255372 and rs7903146 with the polycystic ovary syndrome risk: systemic review and meta-analysis.Journal of ovarian research · 2025Pooled it
- Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis.Scientific reports · 2016Pooled it
- Transcription Factor 7-Like 2 (TCF7L2) rs7903146 Polymorphism as a Risk Factor for Gestational Diabetes Mellitus: A Meta-Analysis.PloS one · 2016Pooled it
- Transcription factor 7-like 2 gene links increased in vivo insulin synthesis to type 2 diabetes.EBioMedicine · 2018Trial
- Trial
- From Genes to Diets: A Critical Review of Genetic, Nutrigenomic and Epigenetic Mechanisms in Type 2 Diabetes Mellitus.Nutrients · 2026Review
- Molecular Mechanisms Associated with Metabolic Dysfunction: Contributions of Nutritional Genomics.Metabolites · 2026Review
- Interactions with polygenic background impact quantitative traits in the UK Biobank.medRxiv : the preprint server for health sciences · 2025Article
- Western Diet Induces Changes in Gene Expression in Multiple Tissues During Early Insulin Resistance and Glucose Intolerance in Male C57BL/6 Mice.Current issues in molecular biology · 2025Article
- Association and haplotype analysis of TCF7L2 gene variants with development of obesity in type 2 diabetic patients among Northern Iranians.Journal of diabetes and metabolic disorders · 2025Article
- Single-cell mRNA-regulation analysis reveals cell type-specific mechanisms of type 2 diabetes.Nature communications · 2025Article
- Diabetes mellitus polygenic risk scores: heterogeneity and clinical translation.Nature reviews. Endocrinology · 2025Review
- Association ofDiagnostics (Basel, Switzerland) · 2025Article
- Identification of Novel Genetic Variants and Food Intake Factors Associated with Type 2 Diabetes in South Korean Adults, Using an Illness-Death Model.International journal of molecular sciences · 2025Article
- A Genetic Clue to T2DM in Bangladesh: TheOman medical journal · 2025Article
- Diabetes-preventive molecular mechanisms of breast versus formula feeding: new insights into the impact of milk on stem cell Wnt signaling.Frontiers in nutrition · 2025Review
- Multi-ancestry GWAS of severe pregnancy nausea and vomiting identifies risk loci associated with appetite, insulin signaling, and brain plasticity.Research square · 2024Article
- Multi-ancestry GWAS of severe pregnancy nausea and vomiting identifies risk loci associated with appetite, insulin signaling, and brain plasticity.medRxiv : the preprint server for health sciences · 2024Article
- Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy.Metabolites · 2024Review
36 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
20 authors at 5 institutions in 4 countries.
Funding
Abstract
Genome-wide association studies have revealed >60 loci associated with type 2 diabetes (T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for its effect on insulin secretion in rodent and human pancreatic islets. ISL1 is a primary target of TCF7L2 and regulates proinsulin production and processing via MAFA, PDX1, NKX6.1, PCSK1, PCSK2 and SLC30A8, thereby providing evidence for a coordinated regulation of insulin production and processing. The risk T-allele of rs7903146 was associated with increased TCF7L2 expression, and decreased insulin content and secretion. Using gene expression profiles of 66 human pancreatic islets donors', we also show that the identified TCF7L2-ISL1 transcriptional network is regulated in a genotype-dependent manner. Taken together, these results demonstrate that not only synthesis of proinsulin is regulated by TCF7L2 but also processing and possibly clearance of proinsulin and insulin. These multiple targets in key pathways may explain why TCF7L2 has emerged as the gene showing one of the strongest associations with T2D.
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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.