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Role of Wnt signaling pathways in type 2 diabetes mellitus

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Abstract

Type 2 diabetes mellitus (T2DM) has become a major global public health issue in the twenty-first century and its incidence has increased each year. Wnt signaling pathways are a set of multi-downstream signaling pathways activated by the binding of Wnt ligands to membrane protein receptors. Wnt signaling pathways regulate protein expression and play important roles in protecting the body's normal physiological metabolism. This review describes Wnt signaling pathways, and then aims to reveal how Wnt signaling pathways participate in the occurrence and development of T2DM. We found that Wnt/c-Jun N-terminal kinase signaling was closely associated with insulin resistance, inflammatory response, and pancreatic β-cell and endothelial dysfunction. β-catenin/transcription factor 7-like 2 (TCF7L2)-mediated and calcineurin/nuclear factor of activated T cells-mediated target genes were involved in insulin synthesis and secretion, insulin degradation, pancreatic β-cell growth and regeneration, and functional application of pancreatic β-cells. In addition, polymorphisms in the TCF7L2 gene could increase risk of T2DM according to previous and the most current results, and the T allele of its variants was a more adverse factor for abnormal pancreatic β-cell function and impaired glucose tolerance in patients with T2DM. These findings indicate a strong correlation between Wnt signaling pathways and T2DM, particularly in terms of pancreatic islet dysfunction and insulin resistance, and new therapeutic targets for T2DM may be identified.

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Acknowledgements

This work was supported by the Key Planned Project of Department of Science & Technology of Liaoning province in 2020 [2020JH2/10200039], and we are gratefully acknowledged.

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Authors and Affiliations

  1. College of Food Science, Shenyang Agricultural University, Dongling Road, No. 120, Shenyang, 110866, Liaoning, People’s Republic of China

    Jing Chen, Jingjing Mu, Dongnan Li & Xianjun Meng

  2. College of Light Industry, Liaoning University, Chongshan Middle Road, No. 66, Shenyang, 110036, Liaoning, People’s Republic of China

    Chong Ning

  3. Center of Experimental Teaching, Shenyang Normal University, Huanghe North Street, No. 253, Shenyang, 110034, Liaoning, People’s Republic of China

    Yan Ma

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  1. Jing Chen
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This literature review was written by XM and JC. Relevant guidance and advice was provided by CN, JM, DL and YM. All authors read and approved the final manuscript.

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Correspondence to Xianjun Meng.

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Chen, J., Ning, C., Mu, J. et al. Role of Wnt signaling pathways in type 2 diabetes mellitus. Mol Cell Biochem 476, 2219–2232 (2021). https://doi.org/10.1007/s11010-021-04086-5

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