Stimulation of IRS-1-associated phosphatidylinositol 3-kinase and Akt/protein kinase B but not glucose transport by beta 1-integrin signaling in rat adipocytes

The signal transduction pathway by which insulin stimulates glucose transpo rt is not understood, but a role for complexes of insulin receptor substrat e (IRS) proteins and phosphatidylinsitol (PI) 3-kinase as well as for Akt/p rotein kinase B (PKB) has been proposed. Here, we present evidence suggesti ng that formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation are insufficient to stimulate glucose transport in rat adipocytes, Cross-linki ng of beta(1)-integrin on the surface of rat adipocytes by anti-beta(1)-int egrin. antibody and fibronectin was found to cause greater IRS-1 tyrosine p hosphorylation, IRS-1-associated PI 3-kinase activity, and Akt/PKB activati on, detected by anti-serine 473 antibody, than did 1 nM insulin. Clustering of beta(1)-integrin also significantly potentiated stimulation of insulin receptor and IRS-1 tyrosine phosphorylation, IRS-associated PI 3-kinase act ivity, and Akt/PKB activation caused by submaximal concentrations of insuli n. In contrast, beta(1)-integrin clustering caused neither a change in deox yglucose transport nor an effect on the ability of insulin to stimulate deo xyglucose uptake at any concentration along the entire dose-response relati onship range. The data suggest that (i) beta(1)-integrins can engage tyrosi ne kinase signaling pathways in isolated fat cells, potentially regulating fat cell functions and (ii) either formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation is not necessary for regulation of glucose transpor t in fat cells or an additional signaling pathway is required.