Insulin promotes the biosynthesis and secretion of apolipoprotein B-48 by altering apolipoprotein B mRNA editing.
Insulin promotes the biosynthesis and secretion of apolipoprotein B-48 by altering apolipoprotein B mRNA editing.
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胰岛素通过改变载脂蛋白 B mRNA 编辑来促进载脂蛋白 B-48 的生物合成和分泌。
DOI：
10.1073/pnas.91.12.5392
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发表时间：
1994
影响因子：
11.1
通讯作者：
Elam,MB
中科院分区：
文献类型：
--
作者：
Thorngate,FE;Raghow,R;Wilcox,HG;Werner,CS;Heimberg,M;Elam,MB
长期胰岛素治疗选择性刺激培养的原代大鼠肝细胞分泌截短形式的载脂蛋白 B (apoB)、apoB-48。长期使用 400 ng/ml 胰岛素治疗会导致 apoB 总分泌量增加 3 倍，其中 apoB-48 约占增量的 75%。 apo-B-48 是通过转录后编辑机制修饰的全长 apoB mRNA 翻译产生的蛋白质产物。编辑将 apoB-100 编码区中部的密码子 2153 从编码谷氨酰胺的 CAA 更改为翻译停止信号 UAA。因此，我们研究了胰岛素治疗对从原代大鼠肝细胞培养物中分离的 RNA 中经过编辑的 apoB mRNA 与未经编辑的 apoB mRNA 的比率的影响。编辑后的 apoB mRNA 与未编辑的 apoB mRNA 的比例发生了巨大的变化，从未处理细胞中的约 1:1 到胰岛素处理细胞中的 7:1。在研究的胰岛素浓度范围（0.4-400 ng/ml）内，胰岛素对 apoB 分泌和 apoB mRNA 编辑产生剂量依赖性影响。相比之下，油酸也增加了apoB（B-48和B-100）的分泌，但对分泌的apoB-48与apoB-100颗粒的比例没有显着影响，并且对编辑的apoB mRNA的比例没有影响。通过 Northern 印迹分析测定，胰岛素和油酸都不影响总 apoB mRNA 水平。这些数据强烈表明胰岛素通过调节编辑的apoB mRNA的比例来刺激大鼠肝细胞中apoB-48的生物合成和分泌。
Long-term insulin treatment selectively stimulates secretion of the truncated form of apolipoprotein B (apoB), apoB-48, from primary rat hepatocytes in culture. Chronic treatment with insulin at 400 ng/ml causes a 3-fold increase in total apoB secretion, with apoB-48 making up about 75% of that increase. apo-B-48 is the protein product generated by translation of full-length apoB mRNA which has been modified by a posttranscriptional editing mechanism. Editing changes codon 2153 in the middle of the apoB-100 coding region from CAA, coding for glutamine, to UAA, a translation stop signal. We therefore examined the effect of insulin treatment on the ratio of edited to nonedited apoB mRNA in RNA isolated from primary rat hepatocyte cultures. There was a dramatic shift in the ratio of edited versus nonedited forms of apoB mRNA, from about 1:1 in untreated cells to 7:1 in insulin-treated cells. Insulin exerted a dose-dependent effect on apoB secretion and apoB mRNA editing over the range of insulin concentrations studied (0.4-400 ng/ml). In contrast, oleic acid, which also increased apoB (B-48 and B-100) secretion, had no significant effect on the ratio of apoB-48 to apoB-100 particles secreted and no effect on the proportion of edited apoB mRNA. Neither insulin nor oleic acid affects total apoB mRNA levels as assayed by Northern blot analysis. These data strongly suggest that insulin stimulates biosynthesis and secretion of apoB-48 in rat hepatocytes by regulating the proportion of edited apoB mRNA.