The effect of insulin on glycogen synthase activity in human diploid fibroblasts has been studied. As little as 2 × 10−10 M insulin increased the glycogen synthase / activity without changing the total activity. Stimulation occurred within 5 minand became maximal in 30 min. A half-maximal increase of / activity was achieved at 3 × 10−9 M insulin. Glucose starvation increased the magnitude of response of glycogen synthase to insulin but did not change the insulin concentration necessary to give a half-maximal stimulation. Glucose increased the basal level of / activity in human diploid fibroblasts; the effect of insulin was additive. During in vitro senescence the total glycogen synthase activity declined, but the concentration of insulin that produced a half-maximal stimulation remained unchanged. These data indicate that regulation of glycogen synthase activity in human diploid fibroblasts is responsive to physiologic insulin levels and that the system provides a useful model for the in vitro study of insulin sensitivity.

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