EFFECTS OF EPINEPHRINE ON INSULIN-STIMULATED GLUCOSE-UPTAKE AND GLUT-4 PHOSPHORYLATION IN MUSCLE

beta-Adrenergic stimulation has been reported to inhibit insulin-stimu lated glucose transport in adipocytes. This effect has been attributed to a decrease in the intrinsic activity of the GLUT-4 isoform of the glucose transporter that is mediated by phosphorylation of GLUT-4. Ear ly studies showed no inhibition of insulin-stimulated glucose transpor t by epinephrine in skeletal muscle. The purpose of this study was to determine the effect of epinephrine on GLUT-4 phosphorylation, and ree valuate the effect of beta-adrenergic stimulation on insulin-activated glucose transport, in skeletal muscle. We found that 1 mu M epinephri ne, which raised adenosine 3',5'-cyclic monophosphate approximately ni nefold, resulted in GLUT-4 phosphorylation in rat skeletal muscle but had no inhibitory effect on insulin-stimulated 3-O-methyl-D-glucose (3 -MG) transport. In contrast to 3-MG transport, the uptakes of 2-deoxyg lucose and glucose were markedly inhibited by epinephrine treatment. T his inhibitory effect was presumably mediated by stimulation of glycog enolysis, which resulted in an increase in glucose 6-phosphate concent ration to levels known to severely inhibit hexokinase. We conclude tha t 1) beta-adrenergic stimulation decreases glucose uptake by raising g lucose 6-phosphate concentration, thus inhibiting hexokinase, but does not inhibit insulin-stimulated glucose transport and 2) phosphorylati on of GLUT-4 has no effect on glucose transport in skeletal muscle.