Previous Article | Next Article ![]()
Molecular and Cellular Biology, October 1999, p. 6765-6774, Vol. 19, No. 10
Department of Medicine,
Received 19 May 1999/Returned for modification 24 June
1999/Accepted 2 July 1999
We evaluated the role of the G alpha-q (G
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
G Alpha-q/11 Protein Plays a Key Role in
Insulin-Induced Glucose Transport in 3T3-L1 Adipocytes
q) subunit of
heterotrimeric G proteins in the insulin signaling pathway leading to
GLUT4 translocation. We inhibited endogenous G
q function by single
cell microinjection of anti-G
q/11 antibody or RGS2 protein (a GAP
protein for G
q), followed by immunostaining to assess GLUT4
translocation in 3T3-L1 adipocytes. G
q/11 antibody and RGS2
inhibited insulin-induced GLUT4 translocation by 60 or 75%, respectively, indicating that activated G
q is important for
insulin-induced glucose transport. We then assessed the effect of
overexpressing wild-type G
q (WT-G
q) or a constitutively active
G
q mutant (Q209L-G
q) by using an adenovirus expression vector. In
the basal state, Q209L-G
q expression stimulated
2-deoxy-D-glucose uptake and GLUT4 translocation to 70% of
the maximal insulin effect. This effect of Q209L-G
q was inhibited by
wortmannin, suggesting that it is phosphatidylinositol 3-kinase
(PI3-kinase) dependent. We further show that Q209L-G
q stimulates
PI3-kinase activity in p110
and p110
immunoprecipitates by 3- and
8-fold, respectively, whereas insulin stimulates this activity mostly
in p110
by 10-fold. Nevertheless, only microinjection of
anti-p110
(and not p110
) antibody inhibited both insulin- and
Q209L-G
q-induced GLUT4 translocation, suggesting that the metabolic
effects induced by Q209L-G
q are dependent on the p110
subunit of
PI3-kinase. In summary, (i) G
q appears to play a necessary role in
insulin-stimulated glucose transport, (ii) G
q action in the insulin
signaling pathway is upstream of and dependent upon PI3-kinase, and
(iii) G
q can transmit signals from the insulin receptor to the
p110
subunit of PI3-kinase, which leads to GLUT4 translocation.
*
Corresponding author. Mailing address: Dept. of
Medicine (0673), University of California, San Diego, 9500 Gilman Dr.,
La Jolla, CA 92093. Phone: (858) 534-6651. Fax: (858) 534-6653. E-mail: jolefsky{at}ucsd.edu.
Molecular and Cellular Biology, October 1999, p. 6765-6774, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|