ACUTE REGULATION BY INSULIN OF PHOSPHATIDYLINOSITOL-3-KINASE, RAD, GLUT-4, AND LIPOPROTEIN-LIPASE MESSENGER-RNA LEVELS IN HUMAN MUSCLE

We have investigated the acute regulation by insulin of the mRNA level s of nine genes involved in insulin action, in muscle biopsies obtaine d before and at the end of a 3-h euglycemic hyperinsulinemic clamp. Us ing reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor subst rate-1, the p85 alpha subunit of phosphatidylinositol-3-kinase, Ras as sociated to diabetes (Rad), the glucose transporter Glut 4, glycogen s ynthase, 6-phosphofructo-1-kinase, lipoprotein lipase, and the hormone -sensitive lipase. Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56+/-13%), Rad (+96+/-25%), the p85 alpha s ubunit of phosphatidylinositol-3-kinase (+92+/-18%) and a decrease in the lipoprotein lipase mRNA level (-49+/-5%), while the abundance of t he other mRNAs was unaffected. The relative expression of the two insu lin receptor variants was not modified. These results demonstrate an a cute coordinated regulation by insulin of the expression of genes codi ng key proteins involved in its action in human skeletal muscle and su ggest that Rad and the p85 alpha regulatory subunit of phosphatidylino sitol-3-kinase can be added to the list of the genes controlled by ins ulin.