Insulin-glycerolipid mediators and gene expression.
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.
Standaert
M L
ML
James A. Haley Veterans Hospital, Tampa, Florida 33612.
Pollet
R J
RJ
D000818:Animals; D004075:Diglycerides / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000502:physiology*; D008563:Membrane Lipids / Q000096:biosynthesis / Q000235:genetics; D009857:Oncogenes; D009955:Ornithine Decarboxylase / Q000235:genetics; D010703:Phorbol Esters / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D010743:Phospholipids / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D004075:Diglycerides; D007328:Insulin; D008563:Membrane Lipids; D010703:Phorbol Esters; D010712:Phosphatidic Acids; D010743:Phospholipids; D012333:RNA, Messenger; D011494:Protein Kinases; D009955:Ornithine Decarboxylase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)