INCREASED GLYCOGEN ACCUMULATION IN TRANSGENIC MICE OVEREXPRESSING GLYCOGEN-SYNTHASE IN SKELETAL-MUSCLE

To investigate the role of glycogen synthase in controlling glycogen a ccumulation, we generated three lines of transgenic mice in which the enzyme was overexpressed in skeletal muscle by using promoter-enhancer elements derived from the mouse muscle creatine kinase gene, In all t hree lines, expression was highest in muscles composed primarily of fa st-twitch fibers, such as the gastrocnemius and anterior tibialis. In these muscles, glycogen synthase activity was increased by as much as 10-fold, with concomitant increases (up to 5-fold) in the glycogen con tent, The uridine diphosphoglucose concentrations were markedly decrea sed, consistent with the increase in glycogen synthase activity, Level s of glycogen phosphorylase in these muscles increased (up to 3-fold), whereas the amount of the insulin-sensitive glucose transporter 4 eit her remained unchanged or decreased, The observation that increasing g lycogen synthase enhances glycogen accumulation supports the conclusio n that the activation of glycogen synthase, as well as glucose transpo rt, contributes to the accumulation of glycogen in response to insulin in skeletal muscle.