Insulin resistance (IR) is the primary pathological mechanism underlying Type 2 diabetes mellitus (T2DM). Many researches have reported the relationship between chronic inflammation and IR, while the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway is rapidly activated in inflammatory conditions. However, the functional role of ERK1/2 in IR remains to be identified. We here reported that C-Jun activation domain-binding protein-1 (JAB1) was upregulated in IR. In addition, we showed that depletion of JAB1 led to recovery of insulin sensitivity. Given the fact that JAB1 played as an activator of ERK1/2, we assumed JAB1 was involved in IR through ERK pathway. So we assessed the effects of JAB1 knockdown in palmitate acid (PA) treated HepG2 cells. Importantly, JAB1 siRNA blocked the effect of PA-induced activation of ERK1/2. Furthermore, silencing of JAB1 could reduce the release of inflammatory factors, facilitate hepatic glucose uptake and improve lipid metabolism. All these data implicated that JAB1 knockdown might alleviate PA-induced IR through ERK pathway in hepatocytes.

胰岛素抵抗（IR）是2型糖尿病（T2DM）的主要病理机制。许多研究已经报道了慢性炎症与IR之间的关系，而细胞外信号调节激酶1/2（ERK1 / 2）途径在炎症条件下被迅速激活。但是，ERK1 / 2在IR中的功能作用尚待确定。我们在这里报告了C-Jun激活域结合蛋白1（JAB1）在IR中被上调。此外，我们显示出JAB1的消耗导致胰岛素敏感性的恢复。考虑到JAB1作为ERK1 / 2的激活剂，我们假设JAB1通过ERK途径参与了IR。因此，我们评估了棕榈酸（PA）处理的HepG2细胞中JAB1敲低的影响。重要的是，JAB1 siRNA阻断了PA诱导的ERK1 / 2激活的作用。此外，沉默JAB1可以减少炎症因子的释放，促进肝葡萄糖摄取并改善脂质代谢。所有这些数据暗示JAB1敲低可能通过肝细胞中的ERK途径减轻PA诱导的IR。