Transforming growth factor alpha inhibits glycogen synthesis and counteracts the stimulation by insulin in hepatocytes.
Rat transforming growth factor alpha (TGF alpha) inhibits glycogen synthesis in rat and guinea pig hepatocyte cultures and counteracts the stimulation of glycogen deposition and activation of glycogen synthase caused by insulin. The EC50 for inhibition of glycogen deposition was 0.2nM. The inhibition of glycogen synthesis was also observed in the absence of extracellular Ca2+ and was not blocked by indomethacin, suggesting that it is not mediated by production of prostaglandins. Since TGF alpha is produced by hepatocytes during liver regeneration and by macrophages during endotoxin stimulation, it may have an autocrine/paracrine effect on hepatic carbohydrate metabolism in these states, and may account for the low hepatic glycogen levels during liver regeneration and the impaired glucose tolerance associated with sepsis.
Peak
M
M
Department of Medicine, University of Newcastle upon Tyne, U.K.
Agius
L
L
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D007328:Insulin; D016211:Transforming Growth Factor alpha; D006003:Glycogen; D006006:Glycogen Synthase; D002118:Calcium; D007213:Indomethacin