Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration.
Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration.
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TCF7L2在控制葡萄糖稳态，胰腺形态，血管形成和再生中扮演多效性角色。
DOI：
10.1038/s41598-017-09867-x
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发表时间：
2017-08-29
影响因子：
4.6
通讯作者：
Argenton F
中科院分区：
文献类型：
--
作者：
Facchinello N;Tarifeño-Saldivia E;Grisan E;Schiavone M;Peron M;Mongera A;Ek O;Schmitner N;Meyer D;Peers B;Tiso N;Argenton F
2型糖尿病(T2D)是一种以胰岛素分泌受损为特征的疾病。Wnt信号转录因子TCF7L2是迄今为止对疾病易感性影响最大的T2D相关基因。然而，TCF7L2变异体影响β细胞胰岛素释放的机制尚不完全清楚。通过利用TCF7L2斑马鱼突变系，我们首先证明了这些动物的特征是高血糖和胰岛发育受损。此外，我们还证明斑马鱼TCF7L2基因在胰腺外分泌中高表达，提示旁观者对β细胞的生长、分化和再生有潜在的影响。最后，我们描述了TCF7L2突变幼虫的一种特殊的血管表型，其特征是胰岛毛细血管的平均数量和直径显著减少。总体而言，斑马鱼TCF7L2突变体具有高血糖、胰腺和血管缺陷以及再生减少的特征，被证明是研究TCF7L2的作用机制和多效性作用的合适模型。TCF7L2是在人类群体中最相关的T2D GWAs。
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.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.8
作者：
Gleeson, M.;Connaughton, V.;Arneson, L. S.
通讯作者：
Arneson, L. S.
影响因子：
158.5
作者：
Florez, Jose C.;Jablonski, Kathleen A.;Altshuler, David
通讯作者：
Altshuler, David
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4
作者：
Columbus, Joshua;Chiang, YuTing;Jin, Tianru
通讯作者：
Jin, Tianru