Overexpression of FoxO1 causes proliferation of cultured pancreatic beta cells exposed to low nutrition.
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.
Ai
Jianzhong
J
Core Facility of Genetically Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
Duan
Jingjing
J
Lv
Xiaoyan
X
Chen
Mianzhi
M
Yang
Qiutan
Q
Sun
Huan
H
Li
Qingwei
Q
Xiao
Yan
Y
Wang
Yidong
Y
Zhang
Zheng
Z
Tan
Ruizhi
R
Liu
Yuhang
Y
Zhao
Danhua
D
Chen
Tielin
T
Yang
Yang
Y
Wei
Yuquan
Y
Zhou
Qin
Q
D049109:Cell Proliferation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
D016895:Culture Media, Serum-Free; D051858:Forkhead Transcription Factors; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases