The involvement of the wnt signaling pathway and TCF7L2 in diabetes mellitus: The current understanding, dispute, and perspective.
The involvement of the wnt signaling pathway and TCF7L2 in diabetes mellitus: The current understanding, dispute, and perspective.
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DOI：
10.1186/2045-3701-2-28
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发表时间：
2012-08-14
影响因子：
7.5
通讯作者：
Jin T
中科院分区：
文献类型：
--
作者：
Ip W;Chiang YT;Jin T
Wnt信号通路最初因其在果蝇和其他真核生物的肿瘤发生和发育中的作用而被发现。该通路的关键效应子是二分转录因子 β-cat/TCF，由游离 β-catenin (β-cat) 和 TCF 蛋白（包括 TCF7L2）形成。最近的广泛研究强调了 Wnt 信号通路在代谢稳态中的作用及其对糖尿病和其他代谢疾病的影响。全基因组关联研究表明，Wnt 信号通路的几个关键组成部分与代谢稳态和 2 型糖尿病 (T2D) 的发展有关。尽管关于 Wnt 信号传导在胰岛发育和功能中的作用的观察存在争议，但 TCF7L2 的某些单核苷酸多态性与 T2D 易感性之间关联的发现推动了探索 Wnt 信号传导在胰腺 β 细胞功能和葡萄糖稳态中的作用的巨大努力。本文介绍了我们对经典Wnt信号通路的基本认识，总结了目前对其在代谢稳态和T2D中的影响的认识，讨论了TCF7L2作为T2D易感基因的工作，并介绍了Wnt信号通路和TCF7L2在胰岛中备受争议的作用以及它们在其他器官中的潜在代谢功能。然后，我们将视野扩展到 Wnt、胰岛素和 FOXO 信号级联之间的串扰，这进一步说明了 Wnt 信号通路在代谢稳态中的复杂性。最后，我们提出了我们的观点。
The Wnt signaling pathway was initially discovered for its role in tumorigenesis and the development of Drosophila and other eukaryotic organisms. The key effector of this pathway, the bipartite transcription factor β-cat/TCF, is formed by free β-catenin (β-cat) and a TCF protein, including TCF7L2. Extensive recent investigations have highlighted the role of the Wnt signaling pathway in metabolic homeostasis and its implication in diabetes and other metabolic diseases. Genome-wide association studies have shown that several key components of the Wnt signaling pathway are implicated in metabolic homeostasis and the development of type 2 diabetes (T2D). Despite controversial observations regarding the role of Wnt signaling in the development and function of pancreatic islets, the discovery of the association between certain single nucleotide polymorphisms of TCF7L2 and T2D susceptibility has fueled great efforts to explore the role of Wnt signaling in the function of pancreatic β-cells and glucose homeostasis. Here we have introduced our basic understanding of the canonical Wnt signaling pathway, summarized our current knowledge on its implication in metabolic homeostasis and T2D, discussed the work on TCF7L2 as a T2D susceptibility gene, and presented the controversial role of Wnt signaling and TCF7L2 in pancreatic islets as well as their potential metabolic function in other organs. We then expanded our view into the crosstalk among Wnt, insulin and FOXO signaling cascades, which further illustrates the complexity of the Wnt signaling pathway in metabolic homeostasis. Finally, we have presented our perspectives.
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