Figure 3.

Oxidative stress plays critical roles in β cell cycle. On cell-cycle regulators, accumulated ROS in beta cells suppressed the expression of cyclins D1 and D2, as well as increased cell-cycle inhibitors such as p21 and p27, leading to decreased β cell proliferation rate. Meanwhile, ROS promoted nuclear the translocation/activation of FoxO1, which in turn prevents β cell replication through the inhibition of Pdx-1 and possibly other β cell-related gene transcriptions. Furthermore, ROS also directly downregulates transcription factors such as Pdx-1, MafA, Nkx6.1, and Ngn3 that are crucial in beta cell proliferation and differentiation.