Translational control of glucose-induced insulin biosynthesis

葡萄糖诱导的胰岛素合成对血糖水平的稳态至关重要，并受转录、翻译和分泌的调节。在本研究中，我们将人胰岛素mRNA的几个长度的5 ' -非翻译区与蛋白质不稳定序列（PEST序列）融合。然后，我们将融合基因导入葡萄糖敏感的人胰岛素产生细胞（1.1B4细胞），并通过翻译确定葡萄糖诱导的胰岛素前合成所必需的mRNA序列。人类胰岛素mRNA的5 ' -非翻译区“GUCCUUCUG”序列被认为是葡萄糖诱导的胰岛素前合成的翻译控制所必需的序列。人类（Homo sapiens sapiens）序列在黑猩猩（Pan troglodytes）、大鼠（Rattus norvegicus）、小鼠（Mus musculus）、豚鼠（Cavia Porcellus）、猪（Sus scrofa domesticus）、牛（Bos taurus）、鸡（Gallus Gallus domesticus）、豹蛙（Rena pipiens）和斑马鱼（Danio rerio）胰岛素mrna中高度保守；序列“nyynsyynr”被认为是葡萄糖诱导的胰岛素生物合成翻译控制的共识序列。

Glucose-induced insulin synthesis is important for homeostasis of blood glucose level and regulated by transcription, translation, and secretion. In the present study, we fused several lengths of 5’-untranslated region of human insulin mRNA with protein-destabilization sequence (PEST sequence). We then introduced the fused genes into glucose-sensitive human insulin producing cells (1.1B4 cells) and determined mRNA sequence essential for glucose-induced pro-insulin synthesis by translation. The sequence “GUCCUUCUG” in the 5’-untranslated region of human insulin mRNA was indicated as a sequence essential for translational control of glucose-induced pro-insulin synthesis. The human (Homo sapiens sapiens) sequence was highly conserved in chimpanzee (Pan troglodytes), rat (Rattus norvegicus), mouse (Mus musculus), guinea pig (Cavia Porcellus), pig (Sus scrofa domesticus), bovine(Bos taurus), chicken (Gallus gallus domesticus), leopard frog (Rena pipiens), and zebrafish (Danio rerio) insulin mRNAs; The sequence “NYNSYYNR “ was suggested as consensus sequence for glucose-induced translational control of insulin biosynthesis.