Triiodo-L-thyronine stimulates glycogen synthesis in rat hepatocyte cultures

The hyperthyroid state is associated with low hepatic glycogen levels, but paradoxically with a high activity of glycogen synthase and low activity of glycogen phosphorylase. We determined the effects of triiodo-L-thyronine (T₃) on glycogen synthesis and glycogen synthase activity in rat hepatocytesin vitro. Culture of rat hepatocytes with T₃ (100 nM–1 M) for 16 h–40 h increases glycogen synthesis from glucose and gluconeogenic precursors. The stimulation of glycogen synthesis by T₃ was associated with an increase in the activity of glycogen synthase and was additive with the long-term effects of insulin but not with the short-term stimulation of glycogen synthesis by insulin. Culture of hepatocytes with T₃ (at concentrations up to 1 M) did not affect the responsiveness of glycogen synthesis to short-term stimulation by insulin but culture with 10 M-T₃ decreased the responsiveness to insulin without affecting the basal rate. It is suggested that the high activity of glycogen synthase in the hyperthyroid state is due to a direct effect of T₃ on the hepatocyte, but the low hepatic glycogen content is probably due to either secondary metabolite and/or endocrine changes or to impaired responsiveness to insulin. T₃ may have an anabolic role in the control of hepatic glycogen storage in the euthyroid postprandial state. (Mol Cell Biol120: 151–158, 1993)Abbreviations T₃ triiodo-L-thyronine