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Molecular and Cellular Biology, November 1999, p. 7771-7781, Vol. 19, No. 11
Centre for Molecular and Cellular Biology and
Department of Physiology and Pharmacology,
Received 21 June 1999/Returned for modification 23 July
1999/Accepted 19 August 1999
Insulin stimulates glucose uptake into muscle and fat cells by
promoting the translocation of glucose transporter 4 (GLUT4) to the
cell surface. Phosphatidylinositide 3-kinase (PI3K) has been implicated
in this process. However, the involvement of protein kinase B
(PKB)/Akt, a downstream target of PI3K in regulation of GLUT4
translocation, has been controversial. Here we report that
microinjection of a PKB substrate peptide or an antibody to PKB
inhibited insulin-stimulated GLUT4 translocation to the plasma membrane
by 66 or 56%, respectively. We further examined the activation of PKB
isoforms following treatment of cells with insulin or platelet-derived
growth factor (PDGF) and found that PKB
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
A Role for Protein Kinase B
/Akt2 in
Insulin-Stimulated GLUT4 Translocation in Adipocytes
is preferentially expressed
in both rat and 3T3-L1 adipocytes, whereas PKB
expression is
down-regulated in 3T3-L1 adipocytes. A switch in growth factor response
was also observed when 3T3-L1 fibroblasts were differentiated into
adipocytes. While PDGF was more efficacious than insulin in stimulating
PKB phosphorylation in fibroblasts, PDGF did not stimulate PKB
phosphorylation to any significant extent in adipocytes, as assessed by
several methods. Moreover, insulin, but not PDGF, stimulated the
translocation of PKB to the plasma membrane and high-density
microsome fractions of 3T3-L1 adipocytes. These results support a role
for PKB in insulin-stimulated glucose transport in adipocytes.
*
Corresponding author. Mailing address: Centre for
Molecular and Cellular Biology and Department of Physiology and
Pharmacology, University of Queensland, Brisbane, Queensland 4072, Australia. Phone: 61 7 3365 4986. Fax: 61 7 3365 4388. E-mail:
D.James{at}cmcb.uq.edu.au.
Molecular and Cellular Biology, November 1999, p. 7771-7781, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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