| First Author | Cooney GJ | Year | 2004 |
| Journal | EMBO J | Volume | 23 |
| Issue | 3 | Pages | 582-93 |
| PubMed ID | 14749734 | Mgi Jnum | J:87892 |
| Mgi Id | MGI:3028438 | Doi | 10.1038/sj.emboj.7600082 |
| Citation | Cooney GJ, et al. (2004) Improved glucose homeostasis and enhanced insulin signalling in Grb14-deficient mice. EMBO J 23(3):582-93 |
| abstractText | 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. |
