Glycogen synthase localization and activity in rat skeletal muscle is strongly dependent on glycogen content

1. The influence of muscle glycogen content on glycogen synthase (GS) local ization and GS activity was investigated in skeletal muscle from male Wista r rats. 2. Two groups of rats were obtained, preconditioned with a combination of e xercise and diet to obtain either high (HG) or low (LG) muscle glycogen con tent. The cellular distribution of GS was studied using subcellular fractio nation and confocal microscopy of immunostained single muscle fibres. Stimu lation of GS activity in HG and LG muscle was obtained with insulin or cont ractions in the perfused rat hindlimb model. 3. We demonstrate that GS translocates from a glycogen-enriched membrane fr action to a cytoskeleton fraction when glycogen levels are decreased. Confo cal microscopy supports the biochemical observations that the subcellular l ocalization of GS is influenced by muscle glycogen content. GS was not foun d in the nucleus. 4. Investigation of the effect of glycogen content on GS activity in basal and insulin- and contraction-stimulated muscle shows that glycogen has a st rong inhibitory effect on GS activity. Our data demonstrate that glycogen i s a more potent regulator of glycogen synthase activity than insulin. Furth ermore we show that the contraction-induced increase in GS activity is mere ly a result of a decrease in muscle glycogen content. 5. In conclusion, the present study shows that GS localization is influence d by muscle glycogen content and that not only basal but also insulin- and contraction-stimulated GS activity is strongly regulated hy glycogen conten t in skeletal muscle.