| First Author | Bergeron S | Year | 2011 |
| Journal | Endocrinology | Volume | 152 |
| Issue | 12 | Pages | 4581-8 |
| PubMed ID | 21952243 | Mgi Jnum | J:179101 |
| Mgi Id | MGI:5301066 | Doi | 10.1210/en.2011-1268 |
| Citation | Bergeron S, et al. (2011) Inhibition of the protein tyrosine phosphatase SHP-1 increases glucose uptake in skeletal muscle cells by augmenting insulin receptor signaling and GLUT4 expression. Endocrinology 152(12):4581-8 |
| abstractText | The protein tyrosine phosphatase (PTPase) Src-homology 2-domain-containing phosphatase (SHP)-1 was recently reported to be a novel regulator of insulin's metabolic action. In order to examine the role of this PTPase in skeletal muscle, we used adenovirus (AdV)-mediated gene transfer to express an interfering mutant of SHP-1 [dominant negative (DN)SHP-1; mutation C453S] in L6 myocytes. Expression of DNSHP-1 increased insulin-induced Akt serine-threonine kinase phosphorylation and augmented glucose uptake and glycogen synthesis. Pharmacological inhibition of glucose transporter type 4 (GLUT4) activity using indinavir and GLUT4 translocation assays revealed an important role for this transporter in the increased insulin-induced glucose uptake in DNSHP-1-expressing myocytes. Both GLUT4 mRNA and protein expression were also found to be increased by DNSHP-1 expression. Furthermore, AdV-mediated delivery of DNSHP-1 in skeletal muscle of transgenic mice overexpressing Coxsackie and AdV receptor also enhanced GLUT4 protein expression. Together, these findings confirm that SHP-1 regulates muscle insulin action in a cell-autonomous manner and further suggest that the PTPase negatively modulates insulin action through down-regulation of both insulin signaling to Akt and GLUT4 translocation, as well as GLUT4 expression. |
