目的：探究GALNT2通过激活EGFR信号通路影响胰岛素自身免疫综合征的作用机制。方法：首先在L-02细胞中过表达或者敲低GALNT2，利用western blot检测在EGF刺激诱导下的EGFR磷酸化水平，同时利用凝集素下拉试验检测了EGFR的糖基化水平。随后我们在细胞中过表达GALNT2以及同时加入PI3K抑制剂，利用western blot检测EGFR的下游信号通路PI3K/AKT的激活情况。接下来我们检测了过表达GALNT2以及同时加入PI3K抑制剂时细胞内NADPH/NADP+比率，以及培养基中的葡萄糖和乳酸含量，探索GALNT2对细胞代谢的影响。最后我们在高胰岛素处理的胰岛素抵抗细胞模型中，检测了GALNT2对细胞的葡萄糖摄取能力的影响。结果：过表达GALNT2的细胞在EGF刺激后，EGFR的磷酸化水平升高，并且EGFR的O型糖基化修饰水平也同样升高；而敲低GALNT2的细胞EGFR磷酸化和O型糖基化水平降低。过表达GALNT2的细胞AKT和mTOR的磷酸化水平升高，而同时加入PI3K抑制剂则能够逆转GALNT2的影响，即GALNT2能够通过促进EGFR磷酸化，激活PI3K/AKT信号通路。GALNT2能够提高NADPH/NADP+比率，促进细胞代谢，而同时加入PI3K抑制剂则能够逆转GALNT2的影响。在高胰岛素诱导的胰岛素抵抗细胞模型中，过表达GALNT2提高了PPAR-γ和PEPCK的mRNA水平，提高了葡萄糖摄取能力。结论：GALNT2通过糖基化修饰EGFR，促进了EGFR的磷酸化，激活PI3K/AKT信号通路，从而促进PPAR-γ和PEPCK的表达，促进细胞代谢，减少能量储存，从而可能诱发胰岛素自身免疫综合征。 关键词：GALNT2; EGFR; 胰岛素自身免疫综合征; PI3K/AKT; 胰岛素抵抗

To explore the mechanism of GALNT2 mediated insulin autoimmune syndrome by activating EGFR signaling pathway. Methods: GALNT2 was overexpressed or knocked down in cells. The phosphorylation level of EGFR induced by EGF stimulation was detected by Western blot, and the glycosylation level of EGFR was detected by lectin pull-down test. Then we used Western blot to detect the activation of PI3K/AKT, the downstream signal pathway of EGFR. Next we detected the intracellular NADPH/NADP+ ratio and the contents of glucose and lactic acid in the medium when GALNT2 was overexpressed and PI3K inhibitor was added at the same time, so as to explore the effect of GALNT2 on cell metabolism. Finally, we examined the effect of GALNT2 on glucose uptake in insulin resistant cell model. Results: After EGF stimulation, the phosphorylation level of EGFR increased in GALNT2-overexpressed cells, and the O-glycosylation modification level of EGFR also increased. The levels of EGFR phosphorylation and O-glycosylation decreased in GALNT2 knockdown cells. The phosphorylation levels of AKT and mTOR increased in cells overexpressing GALNT2, while the addition of PI3K inhibitor can reverse the effect of GALNT2. GALNT2 can activate PI3K/AKT signaling pathway by promoting EGFR phosphorylation. GALNT2 can increase the NADPH/NADP+ ratio and promote cell metabolism, while the addition of PI3K inhibitor can reverse the effect of GALNT2. In a hyperinsulinemic-induced insulin resistance cell model, overexpression of galnt2 increased PPAR-γ and PEPCK mRNA levels to improve glucose uptake. Conclusion: GALNT2 modifies EGFR glycosylation, promotes the phosphorylation of EGFR and activates PI3K/AKT signaling pathway. Activated PI3K/AKT pathway increases PPAR-γ and PEPCK expression, promotes cell metabolism and reduces energy storage, which may induce insulin autoimmune syndrome.