Overexpression of FoxO1 causes proliferation of cultured pancreatic β cells exposed to low nutrition

Jianzhong Ai, Jingjing Duan, Xiaoyan Lv, Mianzhi Chen, Qiutan Yang, Huan Sun, Qingwei Li, Yan Xiao, Yidong Wang, Zheng Zhang, Ruizhi Tan, Yuhang Liu, Danhua Zhao, Tielin Chen, Yang Yang, Yuquan Wei, Qin Zhou

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Multiple lines of evidence have shown that the functional defect of pancreatic β cells is the root cause of type 2 diabetes. FoxO1, a key transcription factor of fundamental cellular physiology and functions, has been implicated in this process. However, the underlying molecular mechanism is still largely unknown. Here, we show that the overexpression of FoxO1 promotes the proliferation of cultured pancreatic β cells exposed to low nutrition, while no change in apoptosis was observed compared with the control group. Moreover, by using two specific inhibitors for PI3K andMAPK signaling, we found that FoxO1 might be the downstream transcription factor of these two pathways. Furthermore, a luciferase assay demonstrated that FoxO1 could regulate the expression of Ccnd1 at the transcription level. Collectively, our findings indicated that FoxO1 modulated by both MAPK and PI3K signaling pathways was prone to cause the proliferation, but not the apoptosis, of pancreatic β cells exposed to low nutrition, at least partially, by regulating the expression of Ccnd1 at the transcription level.

Original languageEnglish (US)
Pages (from-to)218-225
Number of pages8
JournalBiochemistry
Volume49
Issue number1
DOIs
StatePublished - Jan 12 2010

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Ai, J., Duan, J., Lv, X., Chen, M., Yang, Q., Sun, H., Li, Q., Xiao, Y., Wang, Y., Zhang, Z., Tan, R., Liu, Y., Zhao, D., Chen, T., Yang, Y., Wei, Y., & Zhou, Q. (2010). Overexpression of FoxO1 causes proliferation of cultured pancreatic β cells exposed to low nutrition. Biochemistry, 49(1), 218-225. https://doi.org/10.1021/bi901414g