CtBP2 ameliorates palmitate-induced insulin resistance in HepG2 cells through ROS mediated JNK pathway.

Abstract Oxidative stress plays a significant role in the development of hepatic insulin resistance, but the underlying molecular mechanisms remain poorly understood. In this study, we discovered that C-terminal-binding protein 2 (CtBP2) level was decreased in insulin resistance. Taking into account the relationship between CtBP family protein (ANGUSTIFOLIA) and reactive oxygen species (ROS) accumulation, we conjectured CtBP2 was involved in insulin resistance through ROS induced stress. In order to verify this hypothesis, we over-expressed CtBP2 in palmitate (PA) treated HepG2 cells. Here, we found that over-expression of CtBP2 ameliorated insulin sensitivity by increasing phosphorylation of glycogen synthase kinase 3β (GSK3β) and protein kinase B (AKT). These data suggest that CtBP2 plays a critical role in the development of insulin resistance. Moreover, CtBP2 reversed the effects of PA on ROS level, lipid accumulation, hepatic glucose uptake and gluconeogenesis. We also found that over-expression of CtBP2 could suppress PA induced c-jun NH2 terminal kinase (JNK) activation. Furthermore, JNK inhibitor SP600125 was shown to promote the effect of CtBP2 on insulin signaling. Thus, we demonstrated that CtBP2 ameliorated PA-induced insulin resistance via ROS-dependent JNK pathway.