Welsh N, Welsh M, Steiner D F, Hellerström C
Department of Medical Cell Biology, Uppsala University, Sweden.
Biochem J. 1987 Aug 15;246(1):245-8. doi: 10.1042/bj2460245.
To extend previous observations on the mechanisms of translational regulation of insulin biosynthesis [Welsh, Scherberg, Gilmore & Steiner (1986) Biochem. J. 235, 459-467], we have now compared the intracellular distributions of insulin mRNA after stimulation of insulin biosynthesis by glucose, leucine or theophylline. In comparison with low glucose (3.3 mM) only, the presence of 10 mM-leucine + 3.3 mM-glucose resulted in the transfer of insulin mRNA from the pool of the uninitiated mRNA to the free polysome/monosome fraction and an increase in the amount of insulin mRNA associated with the microsomal fraction. Islets exposed to 5 mM-theophylline + 3.3 mM-glucose also showed a decreased content of uninitiated insulin mRNA in the cytosol, but these islets showed no increase in insulin mRNA in the microsomal fraction. These results suggest that leucine, a nutrient stimulant of insulin biosynthesis, acts essentially by the same mechanisms as those of glucose, whereas theophylline acts only to stimulate initiation rates.
为扩展先前关于胰岛素生物合成翻译调控机制的观察结果[威尔士、舍尔伯格、吉尔摩和施泰纳(1986年),《生物化学杂志》235卷,459 - 467页],我们现在比较了葡萄糖、亮氨酸或茶碱刺激胰岛素生物合成后胰岛素mRNA的细胞内分布。与仅含低葡萄糖(3.3 mM)相比,10 mM亮氨酸 + 3.3 mM葡萄糖的存在导致胰岛素mRNA从未起始mRNA池转移至游离多核糖体/单核糖体部分,并使与微粒体部分相关的胰岛素mRNA量增加。暴露于5 mM茶碱 + 3.3 mM葡萄糖的胰岛在胞质溶胶中未起始胰岛素mRNA的含量也降低,但这些胰岛微粒体部分的胰岛素mRNA没有增加。这些结果表明,亮氨酸作为胰岛素生物合成的营养刺激物,其作用机制与葡萄糖基本相同,而茶碱仅作用于刺激起始速率。