Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration

Scientific Reports. 2017;7(1):1-16 DOI 10.1038/s41598-017-09867-x

 

Journal Homepage

Journal Title: Scientific Reports

ISSN: 2045-2322 (Online)

Publisher: Nature Publishing Group

LCC Subject Category: Medicine | Science

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


Nicola Facchinello (Department of Biology, University of Padova)

Estefania Tarifeño-Saldivia (Laboratory of Zebrafish Development and Disease Models, GIGA-R, University of Liege)

Enrico Grisan (Department of Information Engineering, University of Padova)

Marco Schiavone (Department of Biology, University of Padova)

Margherita Peron (Department of Biology, University of Padova)

Alessandro Mongera (Department of Biology, University of Padova)

Olivier Ek (Department of Biology, University of Padova)

Nicole Schmitner (Institute of Molecular Biology, CMBI, Leopold-Franzens-University Innsbruck)

Dirk Meyer (Institute of Molecular Biology, CMBI, Leopold-Franzens-University Innsbruck)

Bernard Peers (Laboratory of Zebrafish Development and Disease Models, GIGA-R, University of Liege)

Natascia Tiso (Department of Biology, University of Padova)

Francesco Argenton (Department of Biology, University of Padova)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 20 weeks

 

Abstract | Full Text

Abstract Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on β-cell growth, differentiation and regeneration. Finally, we describe a peculiar vascular phenotype in tcf7l2 mutant larvae, characterized by significant reduction in the average number and diameter of pancreatic islet capillaries. Overall, the zebrafish Tcf7l2 mutant, characterized by hyperglycemia, pancreatic and vascular defects, and reduced regeneration proves to be a suitable model to study the mechanism of action and the pleiotropic effects of Tcf7l2, the most relevant T2D GWAS hit in human populations.