Cigarette smoking and nicotine exposure contributes for aberrant insulin signaling and cardiometabolic disorders.

Cigarette smoking- and nicotine-mediated dysregulation in insulin-signaling pathways are becoming leading health issues associated with morbidity and mortality worldwide. Many cardiometabolic disorders particularly insulin resistance, polycystic ovary syndrome (PCOS), central obesity and cardiovascular diseases are initiated from exposure of exogenous substances which augment by disturbances in insulin signaling cascade. Among these exogenous substances, nicotine and cigarette smoking are potential triggers for impairment of insulin-signaling pathways. Further, this aberrant insulin signaling is associated with many metabolic complications, which consequently give rise to initiation as well as progression of these metabolic syndromes. Hence, understanding the underlying molecular mechanisms responsible for cigarette smoking- and nicotine-induced altered insulin signaling pathways and subsequent participation in several health hazards are quite essential for prophylaxis and combating these complications. In this article, we have focused on the role of nicotine and cigarette smoking mediated pathological signaling; for instance, nicotine-mediated inhibition of nuclear factor erythroid 2-related factor 2 and oxidative damage, elevated cortisol that may promote central obesity, association PCOS and oxidative stress via diminished nitric oxide which may lead to endothelial dysfunction and vascular inflammation. Pathological underlying molecular mechanisms involved in mediating these metabolic syndromes via alteration of insulin signaling cascade and possible molecular mechanism responsible for these consequences on nicotine exposure have also been discussed.