ArticleDiabetologia2014
TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis by regulating beta cell mass.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 86 citations in OpenAlex.
- Genetic Variants Associated with Response to GLP-1 Receptor Agonists in Diabetes and Obesity.Life (Basel, Switzerland) · 2026Review
- 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
- 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
- The Role of Wnt3a/β-Catenin/TCF7L2 Pathway in Diabetes and Cardiorenal Complications.Cardiorenal medicine · 2025Review
- 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
- Dysregulated autophagy at the nexus of type 2 diabetes mellitus and pancreatic cancer pathogenesis.Frontiers in endocrinology · 2025Review
- Genetic Associations ofDiagnostics (Basel, Switzerland) · 2024Article
- Repurposing celecoxib for colorectal cancer targeting via pH-triggered ultra-elastic nanovesicles: Pronounced efficacy through up-regulation of Wnt/β-catenin pathway in DMH-induced tumorigenesis.International journal of pharmaceutics: X · 2024Article
- Autoimmune diseases and risk of gestational diabetes mellitus: a Mendelian randomization study.Acta diabetologica · 2024Article
- Integrating polygenic risk scores in the prediction of gestational diabetes risk in China.Frontiers in endocrinology · 2024Article
- Tcf7l2 in hepatocytes regulates de novo lipogenesis in diet-induced non-alcoholic fatty liver disease in mice.Diabetologia · 2023Article
- Interactions between Intestinal Homeostasis and NADNutrients · 2023Review
- Single Nucleotide Polymorphism at rs7903146 of Transcription Factor 7-like 2 gene Among Subjects with Type 2 Diabetes Mellitus in Myanmar.Journal of the ASEAN Federation of Endocrine Societies · 2023Article
- Review
- Olanzapine Promotes the Occurrence of Metabolic Disorders in Conditional TCF7L2-Knockout Mice.Frontiers in cell and developmental biology · 2022Article
- Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: "The Earlier, the Better" in Therapy with Incretin-Based Medicine.International journal of molecular sciences · 2021Review
- Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History.International journal of molecular sciences · 2021Review
- Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling.International journal of molecular sciences · 2020Review
- Molecular insights into therapeutic promise of targeting of Wnt/β-catenin signaling pathway in obesity.Molecular biology reports · 2020Review
- Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction.Cells · 2020Review
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15 authors at 6 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisCommon genetic variations of the transcription factor 7-like 2 gene (encoded by TCF7L2), one of the T cell factor/lymphoid enhancer-binding factor transcription factors for the converging wingless-type MMTV integration site family (Wnt)/β-catenin signalling pathway, are known to be associated with type 2 diabetes. Individuals with at-risk alleles of TCF7L2 exhibit impaired insulin secretion. Although previous studies using animal models have revealed the existence of a relationship between the Wnt/β-catenin signalling pathway and glucose homeostasis, it remains unclear whether TCF7L2 in the pancreatic beta cells might be causally involved in insulin secretion in vivo. In this study, we investigated the role of TCF7L2 expressed in the pancreatic beta cells in glucose homeostasis.
methodsThree independent groups of genetically engineered mice (DN mice) were generated, in which expression of the dominant-negative form of Tcf7l2 was driven under a rat insulin promoter. Phenotypes of both adult and newborn mice were evaluated. The levels of genes and proteins expressed in isolated islets were determined by reverse transcription-quantitative PCR and western blot analysis, respectively.
resultsAdult DN mice showed impaired glucose tolerance and decreased insulin secretion in both oral and intraperitoneal glucose tolerance tests. Marked reduction of the beta cell area and whole-pancreas insulin content was observed in both the adult and newborn DN mice. Islets from the DN mice showed decreased gene expressions of Ccnd1, Ccnd2, Irs1, Irs2, Ins1, Ins2 and Mafa, consistent with the deleterious effects of the dominant-negative form of Tcf7l2 on beta cell proliferation and insulin production. CONCLUSIONS/
interpretationTCF7L2 expressed in the pancreatic beta cells plays a crucial role in glucose metabolism through regulation of the beta cell mass.
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