Effect of Puromycin and Puromycin Analogues on Glycogen Synthesis in the Isolated Rat Diaphragm1

Abstract In a previous work from this laboratory it was reported that puromycin specifically depressed the insulin‐induced glycogen synthesis in isolated rat diaphragm. In the present work the effect of puromycin on glycogen synthesis has been studied under modified experimental conditions. When glucose as a substrate was excluded from the incubation medium, puromycin depressed the incorporation of14C‐glucose into glycogen in absence of added insulin. To study this effect of puromycin, experiments with puromycin analogues were undertaken. At a concentration of 270 μ/ml puromycin inhibited protein synthesis by more than 0 %. Equimolar concentrations of puromycin aminonucleoside and 6‐dimethylam nopurine caused only slight inhibition of protein synthesis, but depressed the incorporation of14C‐glucose into glycogen to the same degree as puromycin. The results suggest that puromycin influences the synthesis of muscle glycogen by a mechanism not related to the inhibitory efiect of puromycin on protein synthesis. The possibility that puromycin might interfere with the activity of glycogen synthetase is discussed.