Regulation of ER stress response by insulin signaling

观察胰岛素对内质网应激的影响。胰岛素保护内质网应激诱导的细胞死亡，并增加葡萄糖调节蛋白78(GRP78)的mRNA和蛋白水平。胰岛素还通过PI-3K/AKT通路显著增加激活转录因子-4(ATF4)的蛋白水平。胰岛素增加ATF4蛋白的表达不是由于转录或转录上调，而是一种翻译后机制。SiRNA下调ATF4基因可显著抑制胰岛素对GRP78的诱导作用。这些结果表明，胰岛素调节内质网应激诱导的GRP78表达是通过上调ATF4来实现的。

The effect of insulin on endoplasmic reticulum (ER) stress was investigated. Insulin protected cell death induced by ER stress and increased glucose-regulated protein 78 (GRP78) mRNA and protein levels. Insulin also significantly increased activating transcription factor-4 (ATF4) protein level through PI-3 kinase/AKT pathway. The increase of ATF4 protein by insulin was not due to transcriptional or transational up-regulation but to a post-translational mechanism. Knockdown of ATF4 by siRNA significantly inhibited GRP78 induction by insulin. These results indicate that insulin modulated ER stress-induced GRP78 expression occurs via ATF4 up-regulation.