Regulation of p85α phosphatidylinositol-3-kinase expression by peroxisome proliferator-activated receptors (PPARs) in human muscle cells

Regulation of p85 alpha phosphatidylinositol-3-kinase (p85 alpha PI-3K) expression by peroxisome proliferator-activated receptor (PPAR) activators was studied in human skeletal muscle cells. Activation of PPAR gamma or PPAR beta did not modify the expression of p85 alpha PI-3K. In contrast, activation of PPAR alpha increased p85 alpha PI-3K mRNA. This effect was potentiated by 9-cis-retinoic acid, an activator of RXR. Up-regulation of p85 alpha PI-3K gene expression resulted in a rise in p85 alpha PI-3K protein level and in an increase in insulin-induced PI3-kinase activity. According to the role of p85 alpha PI-3K in insulin action, these results suggest that drugs with dual action on both PPAR gamma and PPAR alpha can be of interest for the treatment of insulin resistance. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.