The complex role of Wnt ligands in type 2 diabetes mellitus and related complications

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 14; pp. 6479 - 6495
• Main Authors: Nie, Xiaobo, Wei, Xiaoyun, Ma, Han, Fan, Lili, Chen, Wei‐Dong
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.07.2021; John Wiley and Sons Inc
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Antagonists; canonical Wnt signalling pathway; Cell division; Chronic illnesses; complications; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Diabetic retinopathy; Disease; Genes; Humans; Insulin resistance; Kinases; Ligands; Low Density Lipoprotein Receptor-Related Protein-6 - genetics; Lymphoma; Metabolism; non‐canonical Wnt signalling pathway; Pathogenesis; Proteins; Review; Reviews; Roles; Serine-Arginine Splicing Factors - genetics; Signal transduction; Transcription factors; Wnt protein; Wnt Proteins - classification; Wnt Proteins - genetics; Wnt Signaling Pathway - genetics; Wnt‐based therapeutics; complications; diabetes; Wnt-based therapeutics; canonical Wnt signalling pathway; non-canonical Wnt signalling pathway
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16663

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.