期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 32, 页码 12093-12097出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0604628103
关键词
conditional gene knockout; diabetes; insulin resistance
资金
- NCI NIH HHS [CA089021, P01 CA089021] Funding Source: Medline
- NIDDK NIH HHS [R01 DK055545, DK34834, DK33201, DK55545, R01 DK033201] Funding Source: Medline
- NIGMS NIH HHS [R37 GM041890, GM41890, R01 GM041890] Funding Source: Medline
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 p85 alpha 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 p85 alpha 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据