Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin.

摘要: Significant activity of phosphatidylinositol 3-kinase (PI 3-kinase) was detected in the membrane fractions, or immunoprecipitates prepared with anti-phosphotyrosine antibodies, from rat adipocytes that had been incubated insulin for 20 min. The PI these preparations as well whole cell lysates not treated inhibited by addition wortmannin, a fungal metabolite, to enzyme assay mixture. inhibition dependent on inhibitor concentration IC50 being less than 10 nM and perfect at 100 nM. effect induce mostly abolished, but its effects tyrosine-phosphorylate beta-subunit receptor other cellular substrate proteins including insulin-receptor-substrate-1 were all antagonized, wortmannin added incubation medium. Insulin stimulation 2-deoxyglucose uptake isoproterenol-induced lipolysis observable under same conditions also antagonized range used insulin-susceptible 3-kinase. It is concluded, therefore, activation wortmannin-sensitive plays pivotal role intracellular signaling pathways arising autophosphorylation leading certain metabolic responses.