Control of glycogen synthesis is shared between glucose transport and glycogen synthase in skeletal muscle fibers

The effects of transgenic overexpression of glycogen synthase in different types of fast-twitch muscle fibers were investigated in individual fibers f rom the anterior tibialis muscle. Glycogen synthase was severalfold higher in all transgenic fibers, although the extent of over expression was twofol d greater in type IIB fibers. Effects of the transgene on increasing glycog en and phosphorylase and on decreasing UDP-glucose were also more pronounce d in type IIB fibers. However, in any grouping of fibers having equivalent malate dehydrogenase activity (an index of oxidative potential), glycogen w as higher in the transgenic fibers. Thus increasing synthase is sufficient to enhance glycogen accumulation in all types of fast-twitch fibers. Effect s on glucose transport and glycogen synthesis were investigated in experime nts in which diaphragm, extensor digitorum long-us (EDL), and soleus muscle s were incubated in vitro. Transport was not increased by the transgene in any of the muscles. The transgene increased basal [C-14]glucose into glycog en by 2.5-fold in the EDL, which is composed primarily of IIB fibers. The t ransgene also enhanced insulin-stimulated glycogen synthesis in the diaphra gm and soleus muscles, which are composed of oxidative fiber types. We conc lude that increasing glycogen synthase activity increases the rate of glyco gen synthesis in both oxidative and glycolytic fibers, implying that the co ntrol of glycogen accumulation by insulin in skeletal muscle is distributed between the glucose transport and glycogen synthase steps.