Figure 2:

The ROS-UCP2-OXPHOS axis in the beta cell. Bmal1 has been shown to directly bind and regulate the expression of Nrf2, which is considered the master regulator of antioxidant gene expression. Cyclical expression of Nrf2 in turn drives circadian cycles of reactive oxygen species (ROS) signals. In the inactive phase of the day, ROS-mediated activation of UCP2 uncouples the beta cell mitochondrial electron transport chain, dampening oxidative phosphorylation of ADP to ATP. Reduced ATP production prevents insulin secretion in the inactive phase of the day. As Nrf2 expression is activated by Bmal1, ROS signals are reduced, preventing UCP2 activation and allowing for maximal GSIS capacity in the active phase of the day, when food is anticipated. Created with BioRender.com.