RNA binding protein DDX1 is responsible for fatty acid mediated repression of insulin translation

Previous studies have focused on the combined glucolipoxicity that is presence of high glucose and free fatty acid levels effect on insulin gene expression, but the effect of high FFA and normal glucose level on insulin expression is unkown. Here we observed that palmitate can inhibit insulin translation. And we identified a novel insulin mrna binding protein DDX1 that is responsible for fatty acid mediated insulin translation inhibition. Palmitate treatment causes phosphorylation of DDX1 at S295 and dissociation from insulin mRNA, which decreases insulin translation.既往研究多聚焦于高糖与游离脂肪酸共存所介导的糖脂毒性（glucolipotoxicity）对胰岛素基因表达的影响，但仅高游离脂肪酸（free fatty acid，下文简称FFA）联合正常血糖水平对胰岛素表达的调控效应仍尚不明确。本研究观察到棕榈酸可抑制胰岛素的翻译过程，并鉴定出一种新型胰岛素mRNA结合蛋白DDX1，该蛋白正是脂肪酸诱导的胰岛素翻译抑制的介导因子。实验结果显示，棕榈酸处理可使DDX1在S295位点发生磷酸化，使其与胰岛素mRNA解离，进而降低胰岛素的翻译水平。