Contraction Activates Glycogen Synthase Independently of Initial Glycogen Concentration

Abstract

Muscle contraction activates glycogen synthesis, but the mechanism for activation of glycogen synthase after contractile activity is poorly understood. Glycogen concentration is powerful regulator of glycogen synthase and it has been suggested that reduced glycogen content determines activation of glycogen synthase after contractile activity. PURPOSE: The purpose of the present study was to investigate effects of muscle contraction on glycogen synthesis, glycogen synthase activation and glycogen synthase phosphorylation in muscle with different glycogen concentrations. METHODS: We manipulated the muscle glycogen content to low (94.8 ±5.0 mmol-kg−1; 24-hours fasted rats; n=36), normal (203.8±10.2 mmol-kg1; Free access to chow; n=28), and high (459.3±30.9 mmol-kg−1; 24-hours fasted rats were refed for 24 hours to supercompensate glycogen; n=32). After manipulation, muscles were dissected for in vitro studies, mounted on contraction apparatus, and stimulated electrically for 30 min. Subsequently, glycogen synthesis, glycogen synthase activity, and glycogen synthase Ser645, Ser649, Ser653, Ser657 phosphorylation were assessed. RESULTS: Contraction decreased glycogen content by 120.6±4.7 (n=28) and 131.5±8.4 mmol-kg−1 (n=32) in muscles with normal and high glycogen, respectively. In muscles with low glycogen, glycogen breakdown was reduced to 67.4±5.0 mmol-kg−1(p<0.001; n=28). Rate of glycogen synthesis after contraction was inversely correlated to initial glycogen content. Contraction increased GS activity in all groups (p < 0.001). Interestingly, contraction activated glycogen synthase in muscles with high glycogen (p < 0.01) without dephosphorylation of the sites phosphorylated by GSK-3. Contraction dephosphorylated these sites in muscles with low and normal glycogen. When insulin was present after contraction, an additive effect of insulin on glycogen synthesis and glycogen synthase activation. Interestingly, rate of glycogen synthesis reach the same level in muscles with low and normal glycogen when insulin was present after contraction; so did glycogen synthase fractional activity and glycogen synthase Ser645, Ser649, Ser653, Ser657 phosphorylation. CONCLUSION: Contractile activity is a powerful activator of GS and glycogen synthesis even in muscles high glycogen content. In muscles with high glycogen, glycogen synthase fractional activity was increased without dephosphorylation of the sites phosphorylated by GSK-3, indicating that contraction activates glycogen synthase by dephosphorylation of other sites. Supported by the Research Council of Norway and The Novo Nordisk Foundation.