Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Basic Medical Sciences, People's Hospital of Hebi, Henan University, Kaifeng, China.
Key Laboratory of Molecular Pathology, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot, China.
J Cell Mol Med. 2021 Jul;25(14):6479-6495. doi: 10.1111/jcmm.16663. Epub 2021 May 27.
Type 2 diabetes mellitus (T2DM) is one of the major chronic diseases, whose prevalence is increasing dramatically worldwide and can lead to a range of serious complications. Wnt ligands (Wnts) and their activating Wnt signalling pathways are closely involved in the regulation of various processes that are important for the occurrence and progression of T2DM and related complications. However, our understanding of their roles in these diseases is quite rudimentary due to the numerous family members of Wnts and conflicting effects via activating the canonical and/or non-canonical Wnt signalling pathways. In this review, we summarize the current findings on the expression pattern and exact role of each human Wnt in T2DM and related complications, including Wnt1, Wnt2, Wnt2b, Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt5b, Wnt6, Wnt7a, Wnt7b, Wnt8a, Wnt8b, Wnt9a, Wnt9b, Wnt10a, Wnt10b, Wnt11 and Wnt16. Moreover, the role of main antagonists (sFRPs and WIF-1) and coreceptor (LRP6) of Wnts in T2DM and related complications and main challenges in designing Wnt-based therapeutic approaches for these diseases are discussed. We hope a deep understanding of the mechanistic links between Wnt signalling pathways and diabetic-related diseases will ultimately result in a better management of these diseases.
2 型糖尿病（T2DM）是一种主要的慢性疾病，其患病率在全球范围内急剧上升，可导致一系列严重的并发症。Wnt 配体（Wnts）及其激活的 Wnt 信号通路密切参与调节对 T2DM 及相关并发症的发生和进展至关重要的各种过程。然而，由于 Wnts 的众多家族成员以及通过激活经典和/或非经典 Wnt 信号通路产生的相互矛盾的作用，我们对它们在这些疾病中的作用的理解还相当初步。在这篇综述中，我们总结了关于人类 Wnt 在 T2DM 及相关并发症中的表达模式和确切作用的最新发现，包括 Wnt1、Wnt2、Wnt2b、Wnt3、Wnt3a、Wnt4、Wnt5a、Wnt5b、Wnt6、Wnt7a、Wnt7b、Wnt8a、Wnt8b、Wnt9a、Wnt9b、Wnt10a、Wnt10b、Wnt11 和 Wnt16。此外，还讨论了 Wnt 的主要拮抗剂（sFRPs 和 WIF-1）和核心受体（LRP6）在 T2DM 及相关并发症中的作用，以及为这些疾病设计基于 Wnt 的治疗方法的主要挑战。我们希望对 Wnt 信号通路与糖尿病相关疾病之间的机制联系有更深入的了解，最终将导致更好地管理这些疾病。
