期刊
MOLECULAR MEDICINE REPORTS
卷 5, 期 1, 页码 233-238出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2011.607
关键词
liraglutide; beta cell; proliferation; Akt; FoxO1; p27
资金
- Natural Science Foundation of China [81070659, 81001190]
- Research Fund for the Doctoral Program of Higher Education of China [2009171110054]
- Natural Science Foundation of Guangdong Province of China [1251008901000030]
- Guangzhou Municipality, Guangdong Province, China [2010J-E521]
- Foundation for the Author of Excellent Doctoral Dissertation of Guangdong Province, China [80000-3226201]
- Sun Yat-sen University [80000-3126200-211]
Numerous studies have shown that liraglutide, a modified form of human glucagon-like peptide-1 (GLP-1), increases beta-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 beta-cell proliferation. INS-1 rat insulinoma cells were exposed to two different concentrations of liraglutide. MTT assay was performed to evaluate beta-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-I cells with 10 and 100 nM liraglutide caused beta-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 beta-cell mass by upregulating beta-cell (p)roliferation and that the proliferative action of liraglutide in beta cells was mediated by activation of PI-3K/Akt, which resulted in inactivation of FoxO1 and decreased p27.
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