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Article

Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway

  • Authors:
    • Yu Qin
    • Min Chen
    • Yan Yang
    • Xin‑Rong Zhou
    • Shi‑Ying Shao
    • Dao‑Wen Wang
    • Gang Yuan
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Geriatrics, The First Hospital of Jiangxia, Wuhan, Hubei 430030, P.R. China
  • Pages: 7372-7380
    |
    Published online on: March 14, 2018
       https://doi.org/10.3892/mmr.2018.8737
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Abstract

Liraglutide, a modified form of glucagon‑like peptide‑1 (GLP‑1), is used in the treatment of diabetes mellitus. However, the underlying mechanism by which liraglutide improves liver insulin resistance remains to be elucidated. The proto‑oncogene Wnt (Wnt) signaling pathway has been reported to be associated with glucose and lipid metabolism. Using in vivo and in vitro models of diabetes and insulin resistance, it was investigated whether the beneficial effects of liraglutide on liver glucose metabolism are mediated by the Wnt signaling pathway. The results of the present study demonstrate that body weight, fasting blood glucose, insulin levels and the homeostasis model assessment for insulin resistance were markedly decreased in db/db mice treated with liraglutide compared with control mice. Liraglutide also improved liver morphology and reduced the accumulation of lipid droplets. Furthermore, the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was downregulated, whereas the expression of phosphorylated forkhead box O1, Wnt signaling pathway‑associated molecules, β‑catenin, transcription factor 7‑like 2 and phosphorylated glycogen synthase kinase-3β was upregulated in the liver of mice treated with liraglutide. In the in vitro study, increased gluconeogenesis and decreased glucose uptake rates were observed in insulin resistant hepatocytes; treatment with liraglutide significantly reversed this effect. Furthermore, transfection of insulin resistant hepatocytes with β‑catenin small interfering RNA attenuated the effects of liraglutide, suggesting that liraglutide improves insulin resistance via activating the β‑catenin/Wnt signaling pathway. The results of the present study suggest a novel mechanism underlying liraglutide‑mediated improvements in insulin resistance in the liver. The Wnt signaling pathway may be a potential therapeutic target for the treatment of altered hepatic physiology in insulin resistance.
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Copy and paste a formatted citation
Spandidos Publications style
Qin Y, Chen M, Yang Y, Zhou XR, Shao SY, Wang DW and Yuan G: Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway. Mol Med Rep 17: 7372-7380, 2018.
APA
Qin, Y., Chen, M., Yang, Y., Zhou, X., Shao, S., Wang, D., & Yuan, G. (2018). Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway. Molecular Medicine Reports, 17, 7372-7380. https://doi.org/10.3892/mmr.2018.8737
MLA
Qin, Y., Chen, M., Yang, Y., Zhou, X., Shao, S., Wang, D., Yuan, G."Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway". Molecular Medicine Reports 17.5 (2018): 7372-7380.
Chicago
Qin, Y., Chen, M., Yang, Y., Zhou, X., Shao, S., Wang, D., Yuan, G."Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway". Molecular Medicine Reports 17, no. 5 (2018): 7372-7380. https://doi.org/10.3892/mmr.2018.8737
Copy and paste a formatted citation
x
Spandidos Publications style
Qin Y, Chen M, Yang Y, Zhou XR, Shao SY, Wang DW and Yuan G: Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway. Mol Med Rep 17: 7372-7380, 2018.
APA
Qin, Y., Chen, M., Yang, Y., Zhou, X., Shao, S., Wang, D., & Yuan, G. (2018). Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway. Molecular Medicine Reports, 17, 7372-7380. https://doi.org/10.3892/mmr.2018.8737
MLA
Qin, Y., Chen, M., Yang, Y., Zhou, X., Shao, S., Wang, D., Yuan, G."Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway". Molecular Medicine Reports 17.5 (2018): 7372-7380.
Chicago
Qin, Y., Chen, M., Yang, Y., Zhou, X., Shao, S., Wang, D., Yuan, G."Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway". Molecular Medicine Reports 17, no. 5 (2018): 7372-7380. https://doi.org/10.3892/mmr.2018.8737
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