Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes
Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes
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DOI：
10.1073/pnas.96.24.13656
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发表时间：
1999-11-23
影响因子：
11.1
通讯作者：
Goldstein, JL
中科院分区：
文献类型：
--
作者：
Shimomura, L;Bashmakov, Y;Goldstein, JL
甾醇调节元件结合蛋白（SREBP5）可促进胆固醇和脂肪酸生物合成和摄取酶编码基因的转录。在目前的实验中，我们观察到通过链脲佐菌素治疗导致糖尿病的大鼠肝脏中编码SREBP亚型SREBP-1c的mRNA下降。编码SREBP-1a的mRNA没有变化，SREBP-1a来源于与SREBP-1c相同的基因，但使用不同的启动子。SREBP-1c:1a转录本的比例从对照大鼠的5:1下降到糖尿病动物的0.2:1，下降了25倍。胰岛素治疗6 h后，SREBP-1c mRNA接近正常水平，1c:1a比值增加17倍。这些处理没有改变SREBP-2的mRNA，它是由一个单独的基因编码的。在新分离的大鼠肝细胞中，SREBP-1c mRNA也有选择性地下降，当胰岛素处理时，SREBP-1c mRNA升高。结合最近肝细胞的数据[Foretz， M., Pacot， C., Dugal， I.等]（1999）。细胞。生物学报，19,3760-3768]，目前的体内研究表明，胰岛素可能通过选择性诱导SREBP-1c基因的转录来刺激肝脏脂质合成。
Sterol regulatory element binding proteins (SREBP5) enhance transcription of genes encoding enzymes of cholesterol and fatty acid biosynthesis and uptake. In the current experiments, we observed a decline in the mRNA encoding one SREBP isoform, SREBP-1c, in the livers of rats that were rendered diabetic by treatment with streptozotocin. There was no change in the mRNA encoding SREBP-1a, which is derived from the same gene as SREBP-1c but uses a different promoter. The ratio of SREBP-1c:1a transcripts fell 25-fold from 5:1 in control rats to 0.2:1 in the diabetic animals. The SREBP-1c mRNA rose nearly to normal, and the 1c:1a ratio increased 17-fold when the diabetic rats were treated for 6 h with insulin. These treatments produced no change in the mRNA for SREBP-2, which is encoded by a separate gene. The SREBP-1c mRNA also fell selectively in freshly isolated rat hepatocytes and rose when the cells were treated with insulin. Considered together with recent data an hepatocytes [Foretz, M., Pacot, C., Dugal, I., ef al. (1999) Mel. Cell. Biol. 19, 3760-3768], the current in vivo studies suggest that insulin may stimulate lipid synthesis in the liver by selectively inducing transcription of the SREBP-1c gene.