Standaert M L, Pollet R J
James A. Haley Veterans Hospital, Tampa, Florida 33612.
FASEB J. 1988 Jun;2(9):2453-61. doi: 10.1096/fasebj.2.9.3286349.
Insulin is an anabolic polypeptide hormone with pleiotrophic effects. During the decades since the initial description by Banting and Best, the acute effects of insulin have been widely studied with particular focus on the mechanism or mechanisms of insulin activation of hexose transport and regulation of metabolic enzyme activity. However, recently there has been a major expansion of investigation to include insulin regulation of gene expression with multiple insulin-sensitive specific mRNAs now reported. In this review, we explore the involvement of insulin-induced changes in plasma membrane glycerolipid metabolism in the transmembrane signaling process required for insulin regulation of mRNA levels. Insulin increases diacylglycerol levels in insulin-responsive cells, and synthetic diacylglycerols or their phorbol ester diacylglycerol analogs, such as 4 beta,9 alpha,12 beta,13 alpha, 20-pentahydroxytiglia-1,6-dien-3-one 12 beta-myristate 13-acetate (TPA), mimic insulin regulation of ornithine decarboxylase mRNA, c-fos mRNA, and phosphoenolpyruvate carboxykinase mRNA levels. This suggests that insulin regulation of specific mRNA levels may be mediated by insulin-induced changes in phospholipid metabolism and that diacylglycerol may play a pivotal role in insulin regulation of gene expression.
胰岛素是一种具有多种效应的合成代谢多肽激素。自班廷和贝斯特首次描述胰岛素后的几十年里，人们对胰岛素的急性效应进行了广泛研究，尤其关注胰岛素激活己糖转运以及调节代谢酶活性的一种或多种机制。然而，最近研究范围有了重大扩展，开始涵盖胰岛素对基因表达的调控，现在已有多种胰岛素敏感的特定信使核糖核酸（mRNA）被报道。在这篇综述中，我们探讨了胰岛素诱导的质膜甘油脂质代谢变化在胰岛素调节mRNA水平所需的跨膜信号传导过程中的作用。胰岛素可提高胰岛素反应性细胞中的二酰甘油水平，而合成二酰甘油或其佛波酯二酰甘油类似物，如4β,9α,12β,13α,20 - 五羟基替告皂苷-1,6 - 二烯-3 - 酮12β - 肉豆蔻酸酯13 - 乙酸酯（TPA），可模拟胰岛素对鸟氨酸脱羧酶mRNA、c - fos mRNA和磷酸烯醇式丙酮酸羧激酶mRNA水平的调控。这表明胰岛素对特定mRNA水平的调控可能是由胰岛素诱导的磷脂代谢变化介导的，并且二酰甘油可能在胰岛素对基因表达的调控中起关键作用。
