G alpha-q/11 protein plays a key role in insulin-induced glucose transport in 3T3-L1 adipocytes.

Détails

ID Serval
serval:BIB_DE3B48D4941F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
G alpha-q/11 protein plays a key role in insulin-induced glucose transport in 3T3-L1 adipocytes.
Périodique
Molecular and cellular biology
Auteur⸱e⸱s
Imamura T., Vollenweider P., Egawa K., Clodi M., Ishibashi K., Nakashima N., Ugi S., Adams J.W., Brown J.H., Olefsky J.M.
ISSN
0270-7306
Statut éditorial
Publié
Date de publication
1999
Peer-reviewed
Oui
Volume
19
Numéro
10
Pages
6765-74
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S. - Publication Status: ppublish
Résumé
We evaluated the role of the G alpha-q (Galphaq) subunit of heterotrimeric G proteins in the insulin signaling pathway leading to GLUT4 translocation. We inhibited endogenous Galphaq function by single cell microinjection of anti-Galphaq/11 antibody or RGS2 protein (a GAP protein for Galphaq), followed by immunostaining to assess GLUT4 translocation in 3T3-L1 adipocytes. Galphaq/11 antibody and RGS2 inhibited insulin-induced GLUT4 translocation by 60 or 75%, respectively, indicating that activated Galphaq is important for insulin-induced glucose transport. We then assessed the effect of overexpressing wild-type Galphaq (WT-Galphaq) or a constitutively active Galphaq mutant (Q209L-Galphaq) by using an adenovirus expression vector. In the basal state, Q209L-Galphaq expression stimulated 2-deoxy-D-glucose uptake and GLUT4 translocation to 70% of the maximal insulin effect. This effect of Q209L-Galphaq was inhibited by wortmannin, suggesting that it is phosphatidylinositol 3-kinase (PI3-kinase) dependent. We further show that Q209L-Galphaq stimulates PI3-kinase activity in p110alpha and p110gamma immunoprecipitates by 3- and 8-fold, respectively, whereas insulin stimulates this activity mostly in p110alpha by 10-fold. Nevertheless, only microinjection of anti-p110alpha (and not p110gamma) antibody inhibited both insulin- and Q209L-Galphaq-induced GLUT4 translocation, suggesting that the metabolic effects induced by Q209L-Galphaq are dependent on the p110alpha subunit of PI3-kinase. In summary, (i) Galphaq appears to play a necessary role in insulin-stimulated glucose transport, (ii) Galphaq action in the insulin signaling pathway is upstream of and dependent upon PI3-kinase, and (iii) Galphaq can transmit signals from the insulin receptor to the p110alpha subunit of PI3-kinase, which leads to GLUT4 translocation.
Mots-clé
1-Phosphatidylinositol 3-Kinase, 3T3 Cells, Adipocytes, Animals, Biological Transport, Deoxyglucose, GTP-Binding Protein alpha Subunits, Gq-G11, GTP-Binding Proteins, Glucose, Glucose Transporter Type 4, Insulin, Isoenzymes, Mice, Monosaccharide Transport Proteins, Muscle Proteins, Protein Kinase C, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptor, Insulin, Signal Transduction
Pubmed
Web of science
Création de la notice
25/01/2008 14:06
Dernière modification de la notice
20/08/2019 16:02
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