A new glycogen synthase activity ratio in skeletal muscle - Effects of exercise and insulin

It was recently reported that MnSO4 stimulates glycogen synthase-dependent glucose transfer from UDPglucose into trichloroacetic acid precipitable end ogenous glycoproteins (GSMn(T)) in human muscle extracts. To determine the physiologic significance of this reaction, we compared a new GS activity ra tio, GSMn(T)/GSH(E) (where GSH(E) represents the usual glucose transfer to ethanol precipitable exogenous glycogen by GS at 7.2 mM glucose 6-phosphate ), with the generally used GSL(E)/GSH(E) ratio (where GSL(E) represents glu cose transfer at 0.17 mM glucose 6-P concentration). Biopsies were obtained from the quadriceps femoris muscle of healthy subjects at rest, after 40 m in of bicycle exercise at similar to 65% of maximal oxygen uptake and after isometric contraction at 2/3 maximal force to fatigue (similar to1 min). G SMn(T)/GSH(E) increased from 0.012 +/-0.002 at rest to 0.054 +/-0.008 (P <0 .01) after 40 min of bicycle exercise and the increase in GSMn(T) activity was strongly related to the decrease in endogenous glycogen (i.e., increase in short-chain endogenous glycoproteins) (r=0.90: P <0.05). On the other h and. GSL(E)/GSH(E) did not change significantly after bicycle exercise (res t = 0439 +/-0.04; exercise = 0.58 +/-0.08, P >0.05). GSMn(T)/GSH(E) increas ed from 0.010 +/-0.001 at rest to 0.016 +/-0.002 (P <0.05) after isometric exercise. whereas GSL(E)/GSH(E) decreased from 0.27 +/-0.04 to 0.20 +/-0.02 (P <0.05) under corresponding conditions. Last, insulin, which stimulates glycogen synthesis, also increased GSMn(T)/GSH(E) (1.8-fold, P <0.05), as w ell as GSL(E)/GSH(E) (1.4-fold, P <0.05), in isolated rat soleus muscle. Th ese data indicate that GSMn(T)/GSH(E) is influenced by endogenous substrate availability and covalent modification. Therefore, GSMn(T)/GSH(E) ratio ma y prove to be a useful alternative to other GS activity ratios that only re flect changes in the phosphorylation state of GS. (C) 2001 Elsevier Science Inc. All rights reserved.