白介素-17A对胰岛素信号通路的影响及其机制  

Effect of Interleukin-17A on Insulin Signaling Pathway

作　　者：李燕平[1] 沈天然[1] 陈旭[1] 凌文华[1] LI Yan-ping SHEN Tian-ran CHEN Xu LING Wen-hua(Guangdong Provincial Key Laboratory of Food, Nutrition and Health//Department of Nutrition, School of Public Health, Sun Yatsen University, Guangzhou 510080, China)

机构地区：[1]广东省膳食营养与健康重点实验室//中山大学公共卫生学院营养学系,广东广州510080

出　　处：《中山大学学报（医学科学版）》2016年第6期809-816,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家重点基础研究发展计划(2012CB17506)

摘　　要：【目的】研究白介素-17A在肝细胞脂肪变性的模型中对胰岛素抵抗的作用。【方法】用油酸诱导建立Hep G2细胞脂肪变性模型,在此模型中用白介素-17A作为干预物,研究白介素-17A对胰岛素信号通路的影响及机制。【结果】单纯IL-17A干预时,细胞p-AKT、p-PI3K磷酸化水平并没有明显变化,同时葡萄糖摄入、糖原合成p-GSK3β、糖异生p-FOXO1/G-6-pase/PEPCK和JNK通路上的p-JNK/p-c-jun等也未出现明显变化。而在高脂诱导Hep G2细胞变性模型中,白介素-17A的添加可促使胰岛素抵抗效应的产生,明显抑制细胞的胰岛素信号分子,p-AKT、p-PI3K磷酸化水平显著下降,同时还表现为葡萄糖摄入减少,糖原合成较少,糖异生增加。此外,JNK通路上的p-JNK、p-c-jun磷酸化水平显著升高。【结论】炎症因子白介素-17A可通过激活JNK通路,产生胰岛素抵抗效应,加剧肝细胞脂肪变性。[ Objective] To investigate the effect of interleukin-17A on insulin resistance in hepatocyte steatosis model cells. [ Methods ] The model of hepatocyte steatosis in HepG2 cells was generated by oleie-acid and then cells were treated with or without intedeukin-17A to classify its role in insulin signaling pathway. [Results] No significant change was observed in p-AKT, p-PI3K phosphorylation levels in HepG2 cells treated with IL - 17A alone, so as the glucose uptake, glycogen synthesis of p-GSK3β, gluconeogenesis of p-FOXO1/G-6-pase/PEPCK or p-JNK/p-c-jun in the JNK pathway. However, in high-fat induced fatty degeneration HepG2 cells model, intervention with interleukin-17A further induced insulin resistance effect, sharply inhibited cell insulin signaling molecules, and significantly decreased p-AKT, p-PI3K phosphorylation levels, resulting in decreased glucose intake, glycogen synthesis, and increased gluconeogenesis. In addition, phosphorylation levels ofp-JNK, p-c-jun in the JNK pathway were markedly up-regulated. [Conclusion] Interleukin-17A might exacerbate insulin resistance through the activation of the JNK signaling pathway, and, resulted in aggravating fatty liver cells degeneration.

关 键 词：白介素-17A 非酒精性脂肪性肝病 脂肪变性 胰岛素抵抗 

分 类 号：R575.25[医药卫生—消化系统]