The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells

  • Authors:
    • Donghong Fang
    • Zhimin Huang
    • Hongyu Guan
    • Jianbin Liu
    • Bin Yao
    • Haipeng Xiao
    • Yanbing Li
  • View Affiliations

  • Published online on: September 30, 2011     https://doi.org/10.3892/mmr.2011.607
  • Pages: 233-238
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Abstract

Numerous studies have shown that liraglutide, a modified form of human glucagon-like peptide-1 (GLP-1), increases β-cell mass. However, the underlying molecular mechanisms remain unclear. In the present study, we investigated the role of Akt/FoxO1/p27 signaling in liraglutide‑induced β-cell proliferation. INS-1 rat insulinoma cells were exposed to two different concentrations of liraglutide. MTT assay was performed to evaluate β-cell proliferation. The expression of Akt/FoxO1/p27 was detected by quantitative real-time PCR and Western blotting. The results revealed that in comparison to the non-treatment group, stimulating INS-1 cells with 10 and 100 nM liraglutide caused β-cell proliferation to be significantly enhanced. The mRNA levels of p27 in INS-1 cells declined upon treatment with liraglutide compared to the non-treatment group. Western blot analysis revealed that the phosphorylation of Akt and FoxO1 was markedly elevated following exposure to liraglutide. Moreover, LY294002, a phosphatidylinositol 3-kinase (PI-3K) inhibitor, significantly abrogated liraglutide‑induced effects. Therefore, we conclude that liraglutide increased the β-cell mass by upregulating β-cell proliferation and that the proliferative action of liraglutide in β cells was mediated by activation of PI-3K/Akt, which resulted in inactivation of FoxO1 and decreased p27.

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January 2012
Volume 5 Issue 1

Print ISSN: 1791-2997
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Spandidos Publications style
Fang D, Huang Z, Guan H, Liu J, Yao B, Xiao H and Li Y: The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells. Mol Med Rep 5: 233-238, 2012
APA
Fang, D., Huang, Z., Guan, H., Liu, J., Yao, B., Xiao, H., & Li, Y. (2012). The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells. Molecular Medicine Reports, 5, 233-238. https://doi.org/10.3892/mmr.2011.607
MLA
Fang, D., Huang, Z., Guan, H., Liu, J., Yao, B., Xiao, H., Li, Y."The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells". Molecular Medicine Reports 5.1 (2012): 233-238.
Chicago
Fang, D., Huang, Z., Guan, H., Liu, J., Yao, B., Xiao, H., Li, Y."The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells". Molecular Medicine Reports 5, no. 1 (2012): 233-238. https://doi.org/10.3892/mmr.2011.607