Ameliorative effect of nicotine exposure on insulin resistance is accompanied by decreased cardiac glycogen synthase kinase-3 and plasminogen activator inhibitor-1 during oral oestrogen-progestin therapy

<p><b>Context:</b> Cigarette smoking is considered to be a major risk factor for the development of diabetes and cardiovascular disease. Oestrogen-progestin combined oral contraceptive (COC) use has been associated with adverse cardiometabolic events.</p> <p><b>Objective:</b> We hypothesized that nicotine would ameliorate insulin resistance (IR) that is accompanied by decreased cardiac glycogen synthase kinase-3 (GSK-3) and plasminogen activator inhibitor-1 (PAI-1).</p> <p><b>Methods:</b> Female Wistar rats received (<i>po</i>) low-(0.1 mg/kg) or high-nicotine (1.0 mg/kg) with or without COC containing 5.0 µg levonorgestrel plus 1.0 µg ethinylestradiol daily for 8 weeks.</p> <p><b>Results:</b> Data showed that COC treatment or nicotine exposure led to IR, glucose deregulation, atherogenic dyslipidemia, increased corticosterone, aldosterone, cardiac and circulating GSK-3 values and PAI-1. However, these effects with the exception of corticosterone and aldosterone were ameliorated in COC + nicotine-exposed rats.</p> <p><b>Conclusion:</b> Amelioration of IR induced by COC treatment is accompanied by decreased circulating PAI-1, cardiac PAI-1 and GSK-3 instead of circulating aldosterone and corticosterone.</p>