PRETRANSLATIONAL AND POSTTRANSLATIONAL UP-REGULATION OF MUSCLE-SPECIFIC GLYCOGEN-SYNTHASE IN ATHLETES

Expression of muscle-specific glycogen synthase (GS) and phosphofructo kinase (PFK) was analyzed in seven athletes and eight control subjects who were characterized using the euglycemic, hyperinsulinemic (2 mu.k g(-1).min(-1)) clamp technique in combination with indirect calorimetr y and biopsy sampling of vastus lateralis muscle. In the basal state, total GS activity and half-maximal GS activation by glucose 6-phosphat e (G-6-P) were respectively 34% (P < 0.03) and 50% (P < 0.005) higher in athletes than in control subjects. In parallel, GS mRNA/mu g total RNA in athletes was 40% (P < 0.005) higher. No difference in GS immuno reactive protein abundance was found between the groups. PFK activity and protein levels were respectively 15% (P < 0.05) and 20% (P < 0.02) lower in athletes, whereas no difference was found in the level of PF K mRNA. After 4 h of hyperinsulinemia, total glucose disposal rate (P < 0.005) and both nonoxidative (P < 0.02) and oxidative (P < 0.03) glu cose metabolism were significantly higher in athletes. In parallel, af ter hyperinsulinemia, the relative activation of GS by G-6-P was signi ficantly higher in athletes, whereas total activity and gene expressio n of both GS and PFK were unaffected by insulin. We conclude that athl etes have increased whole body insulin-stimulated nonoxidative glucose metabolism associated with both pretranslational (mRNA) and posttrans lational (enzyme activity) upregulation of GS. However, the immunoreac tive mass of GS is normal, emphasizing that posttranslational regulati on of the GS protein activity is important for the increased glycogen synthesis rate of muscle in endurance-trained individuals.