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 hepatocytes in vitro. Culture of rat hepatocytes with T3 (100 nM-1 microM) 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 microM) did not affect the responsiveness of glycogen synthesis to short-term stimulation by insulin but culture with 10 microM-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.
Betley
S
S
Department of Medicine, Medical School, University of Newcastle upon Tyne, UK.
Peak
M
M
Agius
L
L
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006980:Hyperthyroidism / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism; D013268:Stimulation, Chemical; D014284:Triiodothyronine / Q000494:pharmacology*
D007328:Insulin; D008112:Liver Glycogen; D014284:Triiodothyronine; D003907:Dexamethasone; D006006:Glycogen Synthase; D005947:Glucose