ArticleHuman molecular genetics2015
Evidence of non-pancreatic beta cell-dependent roles of Tcf7l2 in the regulation of glucose metabolism in mice.
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 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Trial
- The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults.Scientific reports · 2022Article
- Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction.International journal of molecular sciences · 2022Review
- An update of the consensus statement on insulin resistance in children 2010.Frontiers in endocrinology · 2022Review
- A model and test for coordinated polygenic epistasis in complex traits.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation.Nature metabolism · 2020Article
- Developmentally regulatedeLife · 2019Article
- TheDiabetes care · 2019Review
- Assessment of TCF7L2 expression after bariatric surgery.PloS one · 2019Article
- Article
- What Can Diabetes-Associated Genetic Variation in TCF7L2 Teach Us About the Pathogenesis of Type 2 Diabetes?Metabolic syndrome and related disorders · 2018Review
- Article
- Teasing Diabetes Apart, One Locus at a Time.Diabetes care · 2018Article
- Article
- The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance.Frontiers in pharmacology · 2018Article
- Pharmacogenetics in type 2 diabetes: precision medicine or discovery tool?Diabetologia · 2017Review
- Obstacles to Translating Genotype-Phenotype Correlates in Metabolic Disease.Physiology (Bethesda, Md.) · 2017Review
- Genetics of Insulin Resistance and the Metabolic Syndrome.Current cardiology reports · 2016Review
- The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis.Molecular metabolism · 2015Article
- Allelic expression imbalance: tipping the scales to elucidate the function of type 2 diabetes-associated loci.Diabetes · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Non-coding variation within TCF7L2 remains the strongest genetic determinant of type 2 diabetes risk in humans. A considerable effort has been placed in understanding the functional roles of TCF7L2 in pancreatic beta cells, despite evidence of TCF7L2 expression in various peripheral tissues important in glucose homeostasis. Here, we use a humanized mouse model overexpressing Tcf7l2, resulting in glucose intolerance, to infer the contribution of Tcf7l2 overexpression in beta cells and in other tissues to the metabolic phenotypes displayed by these mice. Restoring Tcf7l2 expression specifically in beta cells to endogenous levels, in face of its overexpression elsewhere, results in impaired insulin secretion, reduced beta cell number and islet area, corroborating data obtained in humans showing similar phenotypes as a result of manipulations leading to Tcf7l2 loss of function. Interestingly, the persistent overexpression of Tcf7l2 in non-pancreatic tissues results in a significant worsening in glucose tolerance in vivo, indicating that Tcf7l2 overexpression in beta cells does not account for the glucose intolerance in the Tcf7l2 overexpression mouse model. Collectively, these data posit that Tcf7l2 plays key roles in glucose metabolism through actions beyond pancreatic beta cells, and further points to functionally opposing cell-type specific effects for Tcf7l2 on the maintenance of balanced glucose metabolism, thereby urging a careful examination of its role in non-pancreatic tissues as well as its composite metabolic effects across distinct tissues. Uncovering these roles may lead to new therapeutic targets for type 2 diabetes.
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