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Improved glusoce homeostasis and enhanced insulin signalling in Grb 14-deficient mice

Cooney, Gregory J., Lyons, Ruth J., Crettenand, A. Jayne, Jensen, Thomas E., Molero, Juan Carlos, Mitchell, Christopher J., Biden, Trevor J., Ormandy,Christopher J., Jame, David E. and Daly, Roger J. 2004, Improved glusoce homeostasis and enhanced insulin signalling in Grb 14-deficient mice, EMBO journal, vol. 23, no. 3, pp. 582-593, doi: 10.1038/sj.emboj.7600082.

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Title Improved glusoce homeostasis and enhanced insulin signalling in Grb 14-deficient mice
Author(s) Cooney, Gregory J.
Lyons, Ruth J.
Crettenand, A. Jayne
Jensen, Thomas E.
Molero, Juan Carlos
Mitchell, Christopher J.
Biden, Trevor J.
Ormandy,Christopher J.
Jame, David E.
Daly, Roger J.
Journal name EMBO journal
Volume number 23
Issue number 3
Start page 582
End page 593
Publisher Nature Publishing Group
Place of publication Basingstoke, England
Publication date 2004-02-11
ISSN 0261-4189
1460-2075
Keyword(s) Grb7 family
insulin receptor
metabolism
PKB
signal transduction
Summary Gene targeting was used to characterize the physiological role of growth factor receptor-bound (Grb)14, an adapter-type signalling protein that associates with the insulin receptor (IR). Adult male Grb14-/- mice displayed improved glucose tolerance, lower circulating insulin levels, and increased incorporation of glucose into glycogen in the liver and skeletal muscle. In ex vivo studies, insulin-induced 2-deoxyglucose uptake was enhanced in soleus muscle, but not in epididymal adipose tissue. These metabolic effects correlated with tissue-specific alterations in insulin signalling. In the liver, despite lower IR autophosphorylation, enhanced insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and activation of protein kinase B (PKB) was observed. In skeletal muscle, IR tyrosine phosphorylation was normal, but signalling via IRS-1 and PKB was increased. Finally, no effect of Grb14 ablation was observed on insulin signalling in white adipose tissue. These findings demonstrate that Grb14 functions in vivo as a tissue-specific modulator of insulin action, most likely via repression of IR-mediated IRS-1 tyrosine phosphorylation, and highlight this protein as a potential target for therapeutic intervention.
Notes Published online 29 January 2004
Language eng
DOI 10.1038/sj.emboj.7600082
Field of Research 060603 Animal Physiology - Systems
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2004, Nature Publishing Group
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006560

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.