Mu Wan, Cheng Xue-Fang, Liu Ying, Lv Qian-Zhou, Liu Gao-Lin, Zhang Ji-Gang, Li Xiao-Yu
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Pharmacol. 2019 Jan 14;9:1566. doi: 10.3389/fphar.2018.01566. eCollection 2018.
The liver is the central metabolic organ and plays a pivotal role in regulating homeostasis of glucose and lipid metabolism. Aberrant liver metabolism promotes insulin resistance, which is reported to be a common characteristic of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). There is a complex and bidirectional relationship between NAFLD and T2DM. NAFLD patients with hepatic insulin resistance generally share a high risk of impaired fasting glucose associated with early diabetes; most patients with T2DM experience non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and other more severe liver complications such as cirrhosis and hepatocellular carcinoma (HCC). Additionally, hepatic insulin resistance, which is caused by diacylglycerol-mediated activation of protein kinase C epsilon (PKC𝜀), may be the critical pathological link between NAFLD and T2DM. Therefore, this review aims to illuminate current insights regarding the complex and strong association between NAFLD and T2DM and summarize novel and emerging targets for the treatment of hepatic insulin resistance based on established mechanistic knowledge.
肝脏是核心代谢器官，在调节葡萄糖和脂质代谢的稳态中起关键作用。肝脏代谢异常会促进胰岛素抵抗，据报道，胰岛素抵抗是非酒精性脂肪性肝病（NAFLD）和2型糖尿病（T2DM）等代谢性疾病的共同特征。NAFLD与T2DM之间存在复杂的双向关系。患有肝脏胰岛素抵抗的NAFLD患者通常面临与早期糖尿病相关的空腹血糖受损的高风险；大多数T2DM患者会出现非酒精性脂肪肝（NAFL）、非酒精性脂肪性肝炎（NASH）以及其他更严重的肝脏并发症，如肝硬化和肝细胞癌（HCC）。此外，由二酰甘油介导的蛋白激酶Cε（PKCε）激活所引起的肝脏胰岛素抵抗，可能是NAFLD与T2DM之间的关键病理联系。因此，本综述旨在阐明关于NAFLD与T2DM之间复杂而紧密关联的当前见解，并基于已确立的机制知识总结治疗肝脏胰岛素抵抗的新出现的靶点。
