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PMID: 16880400 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 32 ·2006-08-08 ·Pages 12093-7

Taniguchi CM, Tran TT, Kondo T, Luo J, Ueki K, Cantley LC, Kahn CR

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.

MeSH Terms
Animals Diabetes Mellitus/genetics Insulin/metabolism Insulin Resistance Liver/metabolism Mice Mice, Knockout Mice, Transgenic Models, Genetic PTEN Phosphohydrolase/genetics,metabolism,physiology Phenotype Phosphatidylinositol 3-Kinases/chemistry,genetics,physiology
Chemicals
Insulin Phosphatidylinositol 3-Kinases PTEN Phosphohydrolase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Taniguchi Cullen M
Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Tran Thien T
Kondo Tatsuya
Luo Ji
Ueki Kohjiro
Cantley Lewis C
Kahn C Ronald
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0604628103
Published
2006-08-08
Epub
2006-00-31
Pages
12093-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1524929
Subset
IM
Grants
NIDDK NIH HHS · DK34834 · United States
NIDDK NIH HHS · R01 DK055545 · United States
NIGMS NIH HHS · R37 GM041890 · United States
NCI NIH HHS · CA089021 · United States
NIGMS NIH HHS · R01 GM041890 · United States
NIDDK NIH HHS · R01 DK033201 · United States
NIDDK NIH HHS · DK55545 · United States
NIDDK NIH HHS · DK33201 · United States
NCI NIH HHS · P01 CA089021 · United States
NIGMS NIH HHS · GM41890 · United States
Corrections
ErratumIn
PMID: 27330087
External Links
PubMed source DOI: 10.1073/pnas.0604628103 PMC Full Text View journal details
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