ArticleHuman molecular genetics2015
Selective disruption of Tcf7l2 in the pancreatic β cell impairs secretory function and lowers β cell mass.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Pooled it
- Association of the Transcription Factor 7 Like 2 (TCF7L2) Polymorphism With Diabetic Nephropathy Risk: A Meta-Analysis.Medicine · 2016Pooled it
- Diabetes-associated genetic variation in TCF7L2 alters pulsatile insulin secretion in humans.JCI insight · 2020Trial
- Transcription factor 7-like 2 gene links increased in vivo insulin synthesis to type 2 diabetes.EBioMedicine · 2018Trial
- Trial
- CTNNB1 Genetic Variation and Its Interaction With DLK1 in Type 2 Diabetes Mellitus.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- TCF7L2 is essential for the differentiation and invasive function of human extravillous trophoblast.Cellular and molecular life sciences : CMLS · 2025Article
- Molecular mechanism for pancreatic β-cell dysfunction and atherosclerosis and its therapeutic application: Importance of translational research bridging clinical practice and basic research.Journal of diabetes investigation · 2025Review
- Genomics reveals eleven obesity endotypes with distinct biological and phenotypic signatures.medRxiv : the preprint server for health sciences · 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
- Exploring pancreatic beta-cell subgroups and their connectivity.Nature metabolism · 2024Review
- Correlation betweenJournal of Taibah University Medical Sciences · 2024Article
- The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.Genes & diseases · 2024Review
- Mechanisms and Physiological Roles of Polymorphisms in Gestational Diabetes Mellitus.International journal of molecular sciences · 2024Review
- Inhibitory Effect of TCF7L2 on Pancreatic β-Cell Dedifferentiation via ERK/MAPK Signaling Pathway in Diabetes.Clinical medicine insights. Endocrinology and diabetes · 2024Article
- Review
- Controlled SPION-Exosomes Loaded with Quercetin Preserves Pancreatic Beta Cell Survival and Function in Type 2 Diabetes Mellitus.International journal of nanomedicine · 2023Article
- The genetics of bipolar disorder with obesity and type 2 diabetes.Journal of affective disorders · 2022Review
- T-cell factor 7L2 is a novel regulator of osteoblast functions that acts in part by modulation of hypoxia signaling.American journal of physiology. Endocrinology and metabolism · 2022Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
Type 2 diabetes (T2D) is characterized by β cell dysfunction and loss. Single nucleotide polymorphisms in the T-cell factor 7-like 2 (TCF7L2) gene, associated with T2D by genome-wide association studies, lead to impaired β cell function. While deletion of the homologous murine Tcf7l2 gene throughout the developing pancreas leads to impaired glucose tolerance, deletion in the β cell in adult mice reportedly has more modest effects. To inactivate Tcf7l2 highly selectively in β cells from the earliest expression of the Ins1 gene (∼E11.5) we have therefore used a Cre recombinase introduced at the Ins1 locus. Tcfl2(fl/fl)::Ins1Cre mice display impaired oral and intraperitoneal glucose tolerance by 8 and 16 weeks, respectively, and defective responses to the GLP-1 analogue liraglutide at 8 weeks. Tcfl2(fl/fl)::Ins1Cre islets displayed defective glucose- and GLP-1-stimulated insulin secretion and the expression of both the Ins2 (∼20%) and Glp1r (∼40%) genes were significantly reduced. Glucose- and GLP-1-induced intracellular free Ca(2+) increases, and connectivity between individual β cells, were both lowered by Tcf7l2 deletion in islets from mice maintained on a high (60%) fat diet. Finally, analysis by optical projection tomography revealed ∼30% decrease in β cell mass in pancreata from Tcfl2(fl/fl)::Ins1Cre mice. These data demonstrate that Tcf7l2 plays a cell autonomous role in the control of β cell function and mass, serving as an important regulator of gene expression and islet cell coordination. The possible relevance of these findings for the action of TCF7L2 polymorphisms associated with Type 2 diabetes in man is discussed.
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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.