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

Biochemistry
Jianzhong AiQin Zhou

Abstract

Multiple lines of evidence have shown that the functional defect of pancreatic beta 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 beta 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 and MAPK 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 beta cells exposed to low nutrition, at least partially, by regulating the expression of Ccnd1 at the transcription level.

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Citations

Jul 10, 2010·Antioxidants & Redox Signaling·Zhiyong Cheng, Morris F White
May 12, 2012·International Journal of Endocrinology·Elena TarabraMichael Khan
May 4, 2011·Cell Proliferation·X Hu, L C Moscinski
May 21, 2013·Proteomics. Clinical Applications·Xiaoyan LvYuquan Wei
Jun 2, 2015·Bioscience, Biotechnology, and Biochemistry·Xue WangLijun Zhou
Jul 31, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Xiaoxia WangYuqing Dong
Mar 8, 2017·Journal of Diabetes Investigation·Kyoichiro Tsuchiya, Yoshihiro Ogawa
Jan 19, 2021·Physiological Genomics·Shu-Lun JiangDong-Po Xu

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