MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION IS NOT SUFFICIENT FOR STIMULATION OF GLUCOSE-TRANSPORT OR GLYCOGEN-SYNTHASE IN 3T3-L1 ADIPOCYTES

The role of mitogen-activated protein (MAP) kinase in the regulation o f glucose metabolism has been investigated by comparing the effects of insulin and epidermal growth factor (EGF) on MAP kinase activation, g lucose transport, and glycogen synthase in 3T3-L1 adipocytes. Insulin or EGF treatment for 5 min increased p42mapk and p44mapk activity to t he same extent as determined by myelin basic protein kinase activity m easurements and phosphotyrosine immunoblotting. The profiles of myelin basic protein kinase activity following MonoQ chromatography of extra cts obtained from cells incubated with insulin or EGF were almost iden tical. Insulin increased glucose transport and GLUT4 translocation to the cell surface by 15- and 7-fold, respectively. EGF had no significa nt effect on these processes. Insulin increased the glycogen synthase ratio (-Glc-6-P/+Glc-6-P) by 7.5- and 3.5-fold in the presence and abs ence of glucose, respectively. EGF increased the ratios by only 2- and 1.3-fold, respectively. EGF did not appear to inhibit downstream of M AP kinase, because when adipocytes were incubated with insulin plus EG F, the stimulation of glucose transport and glycogen synthase was simi lar to that observed with insulin alone. These findings indicate that activation of the MAP kinase isoforms p42mapk and p44mapk is not suffi cient for the activation of glucose transport and glycogen synthase in 3T3-L1 adipocytes.