title: Overexpression of FoxO1 causes proliferation of cultured pancreatic beta cells exposed to low nutrition.
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.
authors: 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.
authors: Jianzhong
authors: J
authors: Ai
authors: Jingjing
authors: J
authors: Duan
authors: Xiaoyan
authors: X
authors: Lv
authors: Mianzhi
authors: M
authors: Chen
authors: Qiutan
authors: Q
authors: Yang
authors: Huan
authors: H
authors: Sun
authors: Qingwei
authors: Q
authors: Li
authors: Yan
authors: Y
authors: Xiao
authors: Yidong
authors: Y
authors: Wang
authors: Zheng
authors: Z
authors: Zhang
authors: Ruizhi
authors: R
authors: Tan
authors: Yuhang
authors: Y
authors: Liu
authors: Danhua
authors: D
authors: Zhao
authors: Tielin
authors: T
authors: Chen
authors: Yang
authors: Y
authors: Yang
authors: Yuquan
authors: Y
authors: Wei
authors: Qin
authors: Q
authors: Zhou
mesh_terms: 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
chemical_list: D016895:Culture Media, Serum-Free; D051858:Forkhead Transcription Factors; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases