ArticleDiabetologia2012
Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2-null mice.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Pooled it
- CRISPR Technologies in Type 2 Diabetes: From Mechanistic Insights to Therapeutic Discovery.International journal of molecular sciences · 2026Review
- The Placenta in Gestational Diabetes: An Integrated Review on Metabolic Pathways, Genetic, Epigenetic and Ultrasound Biomarkers for Clinical Perspectives.International journal of molecular sciences · 2026Review
- The Role of Wnt3a/β-Catenin/TCF7L2 Pathway in Diabetes and Cardiorenal Complications.Cardiorenal medicine · 2025Review
- 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
- Used Toothbrush as a Potential Source of Gene Expression Among Subjects With Systemic Disease and Adverse Habits.Cureus · 2022Article
- TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut-liver crosstalk.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Olanzapine Promotes the Occurrence of Metabolic Disorders in Conditional TCF7L2-Knockout Mice.Frontiers in cell and developmental biology · 2022Article
- Consequences for Pancreatic β-Cell Identity and Function of Unregulated Transcript Processing.Frontiers in endocrinology · 2021Review
- Adipocyte-specific deletion of Tcf7l2 induces dysregulated lipid metabolism and impairs glucose tolerance in mice.Diabetologia · 2021Article
- A Multi-omic Integrative Scheme Characterizes Tissues of Action at Loci Associated with Type 2 Diabetes.American journal of human genetics · 2020Article
- Tumor-like features of gene expression and metabolic profiles in enlarged pancreatic islets are associated with impaired incretin-induced insulin secretion in obese diabetes: A study of Zucker fatty diabetes mellitus rat.Journal of diabetes investigation · 2020Article
- Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.Frontiers in endocrinology · 2020Review
- Convolutional neural networks for reconstruction of undersampled optical projection tomography data applied to in vivo imaging of zebrafish.Journal of biophotonics · 2019Article
- The developmental Wnt signaling pathway effector β-catenin/TCF mediates hepatic functions of the sex hormone estradiol in regulating lipid metabolism.PLoS biology · 2019Article
- Serotonin is elevated in risk-genotype carriers of TCF7L2 - rs7903146.Scientific reports · 2019Article
- What Can Diabetes-Associated Genetic Variation in TCF7L2 Teach Us About the Pathogenesis of Type 2 Diabetes?Metabolic syndrome and related disorders · 2018Review
- Transcription factor-7-like 2 (The Journal of biological chemistry · 2018Article
- Regulation of Osteoblast Metabolism by Wnt Signaling.Endocrinology and metabolism (Seoul, Korea) · 2018Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisIndividuals carrying type 2 diabetes risk alleles in TCF7L2 display decreased beta cell levels of T cell factor 7 like-2 (TCF7L2) immunoreactivity, and impaired insulin secretion and beta cell sensitivity to glucagon-like peptide 1 (GLP-1). Here, we sought to determine whether selective deletion of Tcf7l2 in mouse pancreas impairs insulin release and glucose homeostasis.
methodsPancreas-specific Tcf7l2-null (pTcf7l2) mice were generated by crossing mice carrying conditional knockout alleles of Tcf7l2 (Tcf7l2-flox) with mice expressing Cre recombinase under the control of the Pdx1 promoter (Pdx1.Cre). Gene expression was assessed by real-time quantitative PCR and beta cell mass by optical projection tomography. Glucose tolerance, insulin secretion from isolated islets, and plasma insulin, glucagon and GLP-1 content were assessed by standard protocols.
resultsFrom 12 weeks of age, pTcf7l2 mice displayed decreased oral glucose tolerance vs control littermates; from 20 weeks they had glucose intolerance upon administration of glucose by the intraperitoneal route. pTcf7l2 islets displayed impaired insulin secretion in response to 17 (vs 3.0) mmol/l glucose (54.6 ± 4.6%, p < 0.01) or to 17 mmol/l glucose plus 100 nmol/l GLP-1 (44.3 ± 4.9%, p < 0.01) compared with control islets. Glp1r (42 ± 0.08%, p < 0.01) and Ins2 (15.4 ± 4.6%, p < 0.01) expression was significantly lower in pTcf7l2 islets than in controls. Maintained on a high-fat (but not on a normal) diet, pTcf7l2 mice displayed decreased expansion of pancreatic beta cell volume vs control littermates. No differences were observed in plasma insulin, proinsulin, glucagon or GLP-1 concentrations. CONCLUSIONS/
interpretationSelective deletion of Tcf7l2 in the pancreas replicates key aspects of the altered glucose homeostasis in human carriers of TCF7L2 risk alleles, indicating the direct role of this factor in controlling beta cell function.
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