Open Access

Fluoxetine regulates glucose and lipid metabolism via the PI3K‑AKT signaling pathway in diabetic rats

  • Authors:
    • Hailong Yang
    • Qiuyun Cao
    • Xiaolu Xiong
    • Peng Zhao
    • Diwen Shen
    • Yuzhe Zhang
    • Ning Zhang
  • View Affiliations

  • Published online on: August 4, 2020     https://doi.org/10.3892/mmr.2020.11416
  • Pages: 3073-3080
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetes mellitus poses a major threat towards global heath due to a lack of effective treatment. Fluoxetine hydrochloride, a selective 5‑hydroxytryptamine reuptake inhibitor, is the most commonly used antidepressant in clinical therapy; however, the potential molecular mechanisms of fluoxetine in diabetes remain unknown. In the present study, reduced glucose, total cholesterol and triglyceride levels and lipid metabolism, as well as upregulated proliferator‑activated receptor γ, fatty acid synthase and lipoprotein lipase, and downregulated sterol regulatory element‑binding protein 1‑c were detected in rats with streptozotocin (STZ)‑induced diabetes following treatment with fluoxetine. Furthermore, fluoxetine significantly inhibited the expression levels of glucose metabolism‑associated proteins in liver tissues, including glycogen synthase kinase 3β (GSK‑3β), glucose‑6 phosphatase catalytic subunit (G6PC), phosphoenolpyruvate carboxykinase (PEPCK) and forkhead box protein O1 (FOXO1). In addition, fluoxetine treatment notably attenuated morphological liver damage in rats with STZ‑induced diabetes. Additionally, fluoxetine could inhibit the phosphatidylinositol 3‑kinase‑protein kinase B (PI3K‑AKT) signaling pathway, whereas LY294002, a specific inhibitor of PI3K, suppressed the function of PI3K‑AKT signaling and suppressed the expression levels of glucose metabolism‑associated proteins, including GSK‑3β, G6PC, PEPCK and FOXO1 in BRL‑3A cells. The results of the present study revealed that fluoxetine may regulate glucose and lipid metabolism via the PI3K‑AKT signaling pathway in diabetic rats.
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October-2020
Volume 22 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yang H, Cao Q, Xiong X, Zhao P, Shen D, Zhang Y and Zhang N: Fluoxetine regulates glucose and lipid metabolism via the PI3K‑AKT signaling pathway in diabetic rats . Mol Med Rep 22: 3073-3080, 2020
APA
Yang, H., Cao, Q., Xiong, X., Zhao, P., Shen, D., Zhang, Y., & Zhang, N. (2020). Fluoxetine regulates glucose and lipid metabolism via the PI3K‑AKT signaling pathway in diabetic rats . Molecular Medicine Reports, 22, 3073-3080. https://doi.org/10.3892/mmr.2020.11416
MLA
Yang, H., Cao, Q., Xiong, X., Zhao, P., Shen, D., Zhang, Y., Zhang, N."Fluoxetine regulates glucose and lipid metabolism via the PI3K‑AKT signaling pathway in diabetic rats ". Molecular Medicine Reports 22.4 (2020): 3073-3080.
Chicago
Yang, H., Cao, Q., Xiong, X., Zhao, P., Shen, D., Zhang, Y., Zhang, N."Fluoxetine regulates glucose and lipid metabolism via the PI3K‑AKT signaling pathway in diabetic rats ". Molecular Medicine Reports 22, no. 4 (2020): 3073-3080. https://doi.org/10.3892/mmr.2020.11416