Phosphoinositide 3-kinase regulatory subunit p85α suppresses insulin action via positive regulation of PTEN Academic Article uri icon


MeSH Major

  • Insulin
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases


  • The phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on liver. Here, we show that mice with a liver-specific deletion of the p85alpha regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin sensitivity. Although PI3K enzymatic activity is diminished in L-Pik3r1KO livers because of a reduced level of regulatory and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually increased. This increased Akt activity correlates with increased phosphatidylinositol (3,4,5)-trisphosphate levels which are due, at least in part, to diminished activity of the (3,4,5)-trisphosphate phosphatase PTEN. Thus, the regulatory subunit p85alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity.

publication date

  • August 8, 2006



  • Academic Article



  • eng

PubMed Central ID

  • PMC1524929

Digital Object Identifier (DOI)

  • 10.1073/pnas.0604628103

PubMed ID

  • 16880400

Additional Document Info

start page

  • 12093

end page

  • 7


  • 103


  • 32