Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes.

ABSTRACT: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of obesity-driven type 2 diabetes mellitus and associated cardiovascular complications. Here, we show that perturbation of caveolar microdomains leads to insulin resistance and concomitant up-regulation of PAI-1 in 3T3L1 adipocytes. We present several lines of evidence showing that the phosphatidylinositol 3-kinase (PI3K) pathway negatively regulates PAI-1 gene expression. Insulin-induced PAI-1 gene expression is up-regulated by a specific inhibitor of PI3K. In addition, serum PAI-1 level is elevated in protein kinase Balpha-deficient mice, whereas it is reduced in p70 ribosomal S6 kinase 1-deficient mice. The PI3K pathway phosphorylates retinoblastoma protein (pRB), known to release free E2 (adenoviral p

SUBMITTER: Venugopal J 

PROVIDER: S-EPMC535371 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature