CONTRASTING ACTION OF SHORT-TERM AND LONG-TERM ADRENALINE INFUSION ON DOG SKELETAL-MUSCLE GLUCOSE-METABOLISM

There are important differences between the short- and long-term effects of adrenaline on determinants of glucose tolerance. To assess this metabolic adaptation at tissue level, the present study examined the effect of acute and prolonged in vivo elevation of adrenaline on glycogen metabolism and glycolysis in skeletal muscle. Adrenaline (50 ng.kg-1.min-1) was infused for 2 h or 74 h and the results compared with 1 h 0.9% NaCl infusion in six trained dogs. Muscle glycogen content was reduced by long-term adrenaline (161 +/- 17 vs NaCl 250 +/- 24-mu-mol/g dry weight; p < 0.05) but not short-term adrenaline (233 +/- 21) indicating a sustained effect of adrenaline on glycogen metabolism. Acutely, glycogen synthase I was reduced (short-term adrenaline 12 +/- 6 vs NaCl 22 +/- 7-mu-mol glycosyl units . g-1 . min-1;p < 0.05) but returned to normal with prolonged adrenaline infusion (20 +/- 5). In contrast, K(m) for glycogen phosphorylase a was not changed acutely (short-term adrenaline 31 +/- 6 vs NaCl 27 +/- 7 mmol/l inorganic phosphate) but was reduced during long-term infusion (19 +/- 4; p <0.05 vs short-term adrenaline). Thus, with short- and long-term adrenaline infusion, there were different enzyme changes, although likely to promote glycogenolysis in both cases. In the glycolytic pathway the substrates glucose 6-phosphate and fructose 6-phosphate did not change significantly and hexokinase was not inhibited. Acutely, phosphofructokinase had reduced V(max) (short-term adrenaline 34 +/- 6 vs NaCl 44 +/- 5 U/g; p < 0.05) but was still above the maximal operating rate in vivo. With prolonged adrenaline infusion, the K(m) for phosphofructokinase was reduced (long-term adrenaline 0.32 +/- 0.03 vs NaCl 0.44 +/- 0.07 mmol/l fructose 6-phosphate; p < 0.05). In this situation of relatively low glycolytic flux, the sustained glycogenolytic effect of prolonged adrenaline infusion mediated by increased glycogen phosphorylase a ctivity occurs without a significant accumulation of hexose monophosphates or impairment of glycolysis.