Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan.
Department of Pharmaceutical Chemistry, Government College University Faisalabad, Pakistan.
Eur J Pharmacol. 2021 Oct 15;909:174410. doi: 10.1016/j.ejphar.2021.174410. Epub 2021 Aug 8.
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.
吸烟和尼古丁介导的胰岛素信号通路失调正成为全球与发病率和死亡率相关的主要健康问题。许多代谢紊乱疾病，特别是胰岛素抵抗、多囊卵巢综合征(PCOS)、中心性肥胖和心血管疾病，都是由增加胰岛素信号级联紊乱的外源性物质暴露引起的。在外源性物质中，尼古丁和吸烟是损害胰岛素信号通路的潜在诱因。此外，这种异常的胰岛素信号与许多代谢并发症有关，这反过来又导致这些代谢综合征的发生和进展。因此，了解导致吸烟和尼古丁引起的胰岛素信号通路改变以及随后参与多种健康危害的潜在分子机制对于预防和治疗这些并发症至关重要。在本文中，我们重点讨论了尼古丁和吸烟介导的病理信号在其中的作用，例如，尼古丁介导的核因子红细胞 2 相关因子 2抑制和氧化损伤、可能促进中心性肥胖的皮质醇升高、通过减少一氧化氮导致 PCOS 和氧化应激的关联，这可能导致内皮功能障碍和血管炎症。还讨论了通过改变胰岛素信号级联介导这些代谢综合征的潜在分子机制，以及尼古丁暴露可能导致这些后果的可能分子机制。
