Abstract
Aims/hypothesis. Thiazolidinediones are new oral antidiabetic drugs that activate the nuclear receptor PPARγ. Our aim was to identify potential target genes of PPARγ in the human adipocyte in order to clarify how thiazolidinediones improve insulin sensitivity. Methods. The effect of BRL 49 653 (Rosiglitazone) on the mRNA expression of insulin receptor, insulin receptor substrate-1, p85α, p110α and p110β subunits of phosphatidylinositol 3-kinase, Glut 4 and hormone sensitive lipase was examined in isolated adipocytes. Target mRNA levels were determined by RT-competitive PCR. Results. The BRL 49 653 (1 μmol/l) increased the mRNA concentrations of p85αPI-3 K (264 ± 46 vs 161 ± 31 amol/μg total RNA, p = 0.003) whithout affecting the expression of the other mRNAs of interest. This effect was dose-dependent (K0.5 = 5 nmol/l) and was reproduced by a specific activator of RXR, indicating that it was probably mediated by the PPARγ/RXR heterodimer. The BRL 49 653 also increased the amount of p85αPI-3K protein in adipose tissue explants (71 ± 19 %). In addition, BRL 49 653 produced a more than twofold increase in insulin stimulation of phosphatidylinositol 3-kinase activity and significantly enhanced the antilipolytic action of insulin. Conclusion/interpretation. This work demonstrates that the gene of p85αPI-3K is probably a target of PPARγ and that thiazolidinediones can improve insulin action in normal human adipocytes. Although the precise mechanism of action of BRL 49 653 on PI3-Kinase activity is not completely clear, these findings improve our understanding of the insulin-sensitizing effects of the thiazolidinediones, possible drugs for the treatment of Type II (non-insulin-dependent) diabetes mellitus. [Diabetologia (2001) 44: 544–554]
Article PDF
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received: 18 May 2000 and in revised form: 2 January 2001
Rights and permissions
About this article
Cite this article
Rieusset, J., Chambrier, C., Bouzakri, K. et al. The expression of the p85α subunit of phosphatidylinositol 3-Kinase is induced by activation of the peroxisome proliferator-activated receptor γ in human adipocytes. Diabetologia 44, 544–554 (2001). https://doi.org/10.1007/s001250051660
Issue Date:
DOI: https://doi.org/10.1007/s001250051660