| First Author | Shao W | Year | 2015 |
| Journal | Mol Metab | Volume | 4 |
| Issue | 4 | Pages | 344-52 |
| PubMed ID | 25830097 | Mgi Jnum | J:220969 |
| Mgi Id | MGI:5637604 | Doi | 10.1016/j.molmet.2015.01.008 |
| Citation | Shao W, et al. (2015) The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis. Mol Metab 4(4):344-52 |
| abstractText | OBJECTIVE: Disruption of TCF7L2 in mouse pancreatic beta-cells has generated different outcomes in several investigations. Here we aim to clarify role of beta-cell TCF7L2 and Wnt signaling using a functional-knockdown approach. METHODS: Adenovirus-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 betaTCFDN. beta-cell specific TCF7L2DN expression was induced in betaTCFDN by doxycycline feeding. RESULTS: TCF7L2DN expression in Ins-1 cells reduced GSIS, cell proliferation and expression of a battery of genes including incretin receptors and beta-cell transcription factors. Inducing TCF7L2DN expression in betaTCFDN 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 beta-cell gene expression and reduced beta-cell mass. CONCLUSIONS: Our observations support a cell autonomous role for TCF7L2 in pancreatic beta-cells suggested by most, though not all, investigations. betaTCFDN is a novel model for further exploring the role of TCF7L2 in beta-cell genesis and metabolic homeostasis. |
