FIGURE 9.

Proposed model by which peroxynitrite-mediated ATF3 and GCK nitration in ethanol consumption mice modulates β-cell function and glucose homeostasis. Chronic ethanol treatment generates peroxynitrite and ROS and then induces ATF3 and GCK nitration. Induced ATF3 down-regulates GCK expression, and the nitrated GCK is more susceptible to protein ubiquitination and degradation, leading to impaired glucose responsiveness, insulin resistance, and β-cell dysfunction and apoptosis. These serial sequence pathways may promote the progression of diabetes development.