Regulation of glycogen synthesis by amino acids in cultured human muscle cells

Insulin and a number of metabolic factors stimulate glycogen synthesis and the enzyme glycogen synthase. Using human muscle cells we find that glycoge n synthesis is stimulated by treatment of the cells with lithium ions, whic h inhibit glycogen synthase kinase 3. Insulin further stimulates glycogen s ynthesis in the presence of lithium ions, an effect abolished by wortmannin and rapamycin. We report also that amino acids stimulate glycogen synthesi s and glycogen synthase, these effects also being blocked by rapamycin and wortmannin. Amino acids stimulate p70(s6k) and transiently inhibit glycogen synthase kinase 3 without effects on the activity of protein kinase B or t he mitogen-activated protein kinase pathway. Thus, the work reported here d emonstrates that amino acid availability can regulate glycogen synthesis. F urthermore, it demonstrates that glycogen synthase kinase 3 can be inactiva ted within cells independent of activation of protein kinase B and p90(rsk) .