[Expression of the glycogenic response to insulin in cultured fetal hepatocytes]

In the present study, we used primary cultures of fetal rat hepatocytes which are highly suitable for studying the glycogenic effect of insulin and its regulation. After a lag in the period of culture in the presence of cortisol, glycogenic response to insulin developed together with a progressive accumulation of glycogen. When insulin was added, the rate of glycogen synthesis increased, becoming maximal after 2-3 h, due to the activation of the glycogen synthase system already present. Modification of glycogen precursors in the medium did not alter the amplitude of the insulin effect. The glycogenic effect of insulin was unrelated to that of glucose load and occurred after the formation of glucose-1-phosphate. This only happened when the cyclic AMP-dependent glycogenolytic system was not stimulated, since it was suppressed by low doses of glucagon. Insulin effect, which was time-dependent, ceased after 4 h. This corresponded to a desensitization of hepatocytes without any alteration in the specific binding of insulin. These variations in the glycogenic effect of insulin were likely due to different causes; one of these could be the first events following the interaction of insulin with its receptor.