ArticleDiabetes2013
The Wnt signaling pathway effector TCF7L2 controls gut and brain proglucagon gene expression and glucose homeostasis.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 receptor agonist, in African-American people with Type 2 diabetes: a meta-analysis of sub-population data from seven phase III trials.Diabetic medicine : a journal of the British Diabetic Association · 2017Pooled it
- Trial
- Converging TCF7L2 and CDKAL1 pathways in the pathogenesis of type 2 diabetes mellitus.Acta diabetologica · 2026Review
- Building dynamical models of multi-step state transitions from single cell gene expression trajectories.bioRxiv : the preprint server for biology · 2025Article
- Association ofDiagnostics (Basel, Switzerland) · 2025Article
- Current understanding and controversy on brain access of GLP-1 and GLP-1 receptor agonists.Journal of translational internal medicine · 2025Article
- Changes in triglyceride-rich lipoprotein particle profiles in response to one-week on a low fat or Mediterranean diet by TCF7L2 rs7903146 genotype: a randomized crossover dietary intervention trial.Genes & nutrition · 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
- Article
- Interactions between Intestinal Homeostasis and NADNutrients · 2023Review
- Short-term semaglutide treatment improves FGF21 responsiveness in primary hepatocytes isolated from high fat diet challenged mice.Physiological reports · 2023Article
- The genetics of bipolar disorder with obesity and type 2 diabetes.Journal of affective disorders · 2022Review
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Article
- TCF7L2 lncRNA: a link between bipolar disorder and body mass index through glucocorticoid signaling.Molecular psychiatry · 2021Article
- Identification of microRNAs and gene regulatory networks in cleft lip common in humans and mice.Human molecular genetics · 2021Article
- Mechanisms of Nicotine Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- Glucolipotoxicity and GLP-1 secretion.BMJ open diabetes research & care · 2021Article
- Forskolin Protected against Streptozotocin-Induced Diabetic Cardiomyopathy via Inhibition of Oxidative Stress and Cardiac Fibrosis in Mice.BioMed research international · 2021Article
- Metabolic Contributions of Wnt Signaling: More Than Controlling Flight.Frontiers in cell and developmental biology · 2021Review
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13 authors at 3 institutions in 1 country.
Funding
Abstract
The type 2 diabetes risk gene TCF7L2 is the effector of the Wnt signaling pathway. We found previously that in gut endocrine L-cell lines, TCF7L2 controls transcription of the proglucagon gene (gcg), which encodes the incretin hormone glucagon-like peptide-1 (GLP-1). Whereas peripheral GLP-1 stimulates insulin secretion, brain GLP-1 controls energy homeostasis through yet-to-be defined mechanisms. We aim to determine the metabolic effect of a functional knockdown of TCF7L2 by generating transgenic mice that express dominant-negative TCF7L2 (TCF7L2DN) specifically in gcg-expressing cells. The gcg-TCF7L2DN transgenic mice showed reduced gcg expression in their gut and brain, but not in pancreas. Defects in glucose homeostasis were observed in these mice, associated with attenuated plasma insulin levels in response to glucose challenge. The defect in glucose disposal was exacerbated with high-fat diet. Brain Wnt activity and feeding-mediated hypothalamic AMP-activated protein kinase (AMPK) repression in these mice were impaired. Peripheral injection of the cAMP-promoting agent forskolin increased brain β-cat Ser675 phosphorylation and brain gcg expression and restored feeding-mediated hypothalamic AMPK repression. We conclude that TCF7L2 and Wnt signaling control gut and brain gcg expression and glucose homeostasis and speculate that positive cross-talk between Wnt and GLP-1/cAMP signaling is an underlying mechanism for brain GLP-1 in exerting its metabolic functions.
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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.