ArticleMolecular metabolism2015
The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- 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
- Short-term semaglutide treatment improves FGF21 responsiveness in primary hepatocytes isolated from high fat diet challenged mice.Physiological reports · 2023Article
- Metabolic Contributions of Wnt Signaling: More Than Controlling Flight.Frontiers in cell and developmental biology · 2021Review
- A Multi-omic Integrative Scheme Characterizes Tissues of Action at Loci Associated with Type 2 Diabetes.American journal of human genetics · 2020Article
- Glucagon-like peptide-1 receptor mediates the beneficial effect of liraglutide in an acute lung injury mouse model involving the thioredoxin-interacting protein.American journal of physiology. Endocrinology and metabolism · 2020Article
- The developmental Wnt signaling pathway effector β-catenin/TCF mediates hepatic functions of the sex hormone estradiol in regulating lipid metabolism.PLoS biology · 2019Article
- TCF7L2 regulates pancreatic β-cell function through PI3K/AKT signal pathway.Diabetology & metabolic syndrome · 2019Article
- Transcription Factor 7-Like 2 (Diabetes care · 2018Article
- Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration.Scientific reports · 2017Article
- Curcumin represses mouse 3T3-L1 cell adipogenic differentiation via inhibiting miR-17-5p and stimulating the Wnt signalling pathway effector Tcf7l2.Cell death & disease · 2017Article
- Current understanding and dispute on the function of the Wnt signaling pathway effector TCF7L2 in hepatic gluconeogenesis.Genes & diseases · 2016Review
- Wnt9a deficiency discloses a repressive role of Tcf7l2 on endocrine differentiation in the embryonic pancreas.Scientific reports · 2016Article
- Beyond association: A functional role for Tcf7l2 in β-cell development.Molecular metabolism · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDisruption of TCF7L2 in mouse pancreatic β-cells has generated different outcomes in several investigations. Here we aim to clarify role of β-cell TCF7L2 and Wnt signaling using a functional-knockdown approach.
methodsAdenovirus-mediated dominant negative TCF7L2 (TCF7L2DN) expression was conducted in Ins-1 cells. The fusion gene in which TCF7L2DN expression is driven by P TRE3G was utilized to generate the transgenic mouse line TCF7L2DN Tet . The double transgenic line was created by mating TCF7L2DN Tet with Ins2-rtTA, designated as βTCFDN. β-cell specific TCF7L2DN expression was induced in βTCFDN by doxycycline feeding.
resultsTCF7L2DN expression in Ins-1 cells reduced GSIS, cell proliferation and expression of a battery of genes including incretin receptors and β-cell transcription factors. Inducing TCF7L2DN expression in βTCFDN during adulthood or immediately after weaning generated no or very modest metabolic defect, while its expression during embryonic development by doxycycline feeding in pregnant mothers resulted in significant glucose intolerance associated with altered β-cell gene expression and reduced β-cell mass.
conclusionsOur observations support a cell autonomous role for TCF7L2 in pancreatic β-cells suggested by most, though not all, investigations. βTCFDN is a novel model for further exploring the role of TCF7L2 in β-cell genesis and metabolic homeostasis.
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