Roles of PI 3-kinase and Ras on insulin-stimulated glucose transport in 3T3-L1 adipocytes.
The dominant negative p85alpha regulatory subunit (delta p85alpha) of phosphatidylinositol (PI) 3-kinase or dominant negative Ras (N17Ras) was overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated gene transduction system. Functional expression of delta p85alpha and N17Ras was confirmed by marked inhibition of insulin-stimulated PI 3-kinase activity and mitogen-activated protein kinase activity, respectively. N17Ras expression did not affect glucose transport activity, whereas delta p85alpha expression inhibited insulin-stimulated glucose transport with impairment of GLUT-4 translocation, although inhibition of glucose transport activity was less remarkable than that of PI 3-kinase activity in delta p85alpha-expressing cells. Thus the Ras signaling pathway does not play a major part in either translocation or intrinsic activity of glucose transporters, but PI 3-kinase activation, via phosphotyrosyl proteins and heterodimeric PI 3-kinase, plays a pivotal role in insulin-stimulated glucose transport. However, a discrepancy was observed between PI 3-kinase activity and glucose transport activity, suggesting a possibility that a different pathway(s) is involved in insulin-stimulated intrinsic activity of glucose transporters.
Katagiri
H
H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Japan.
Asano
T
T
Inukai
K
K
Ogihara
T
T
Ishihara
H
H
Shibasaki
Y
Y
Murata
T
T
Terasaki
J
J
Kikuchi
M
M
Yazaki
Y
Y
Oka
Y
Y
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D018631:ras Proteins / Q000502:physiology*
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins