Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Taniguchi CM,Tran TT,Kondo T,Luo J,Ueki K,Cantley LC,Kahn CRdoi
10.1073/pnas.0604628103subject
Has Abstractpub_date
2006-08-08 00:00:00pages
12093-7issue
32eissn
0027-8424issn
1091-6490pii
0604628103journal_volume
103pub_type
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