Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
Life Sci. 2024 Sep 15;353:122934. doi: 10.1016/j.lfs.2024.122934. Epub 2024 Jul 30.
The review focused mainly on the pathogenesis of hepatogenous diabetes (HD) in liver cirrhosis (LC). This review reveals parallels between the mechanisms of metabolic dysfunction observed in LC and type II diabetes (T2DM), suggesting a shared pathway leading to HD. It underscores the role of insulin in HD pathogenesis, highlighting key factors such as insulin signaling, glucose metabolism, insulin resistance (IR), and the influence of adipocytes. Furthermore, the impact of adipose tissue accumulation, fatty acid metabolism, and pro-inflammatory cytokines like Tumor necrosis factor-α (TNF-α) on IR are discussed in the context of HD. Altered signaling pathways, disruptions in the endocrine system, liver inflammation, changes in muscle mass and composition, and modifications to the gut microbiota collectively contribute to the complex interplay linking cirrhosis and HD. This study highlights how important it is to identify and treat this complex condition in cirrhotic patients by thoroughly analyzing the link between cirrhosis, IR, and HD. It also emphasizes the vitality of targeted interventions. Cellular and molecular investigations into IR have revealed potential therapeutic targets for managing and preventing HD.
本综述主要聚焦于肝硬化(LC)中肝源性糖尿病(HD)的发病机制。该综述揭示了 LC 中观察到的代谢功能障碍机制与 II 型糖尿病(T2DM)之间的相似之处,表明存在导致 HD 的共同途径。它强调了胰岛素在 HD 发病机制中的作用,突出了胰岛素信号、葡萄糖代谢、胰岛素抵抗(IR)以及脂肪细胞的影响等关键因素。此外,还讨论了脂肪组织积累、脂肪酸代谢以及肿瘤坏死因子-α(TNF-α)等促炎细胞因子对 IR 的影响在 HD 中的作用。改变的信号通路、内分泌系统紊乱、肝脏炎症、肌肉质量和组成的变化以及肠道微生物群的改变共同导致了与肝硬化和 HD 相关的复杂相互作用。这项研究强调了通过深入分析肝硬化、IR 和 HD 之间的联系,识别和治疗肝硬化患者这一复杂病症的重要性。它还强调了靶向干预的活力。对 IR 的细胞和分子研究揭示了管理和预防 HD 的潜在治疗靶点。