Abstract
Rat transforming growth factor α (TGFα) 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 EC 50 for inhibition of glycogen deposition was 0.2nM. The inhibition of glycogen synthesis was also observed in the absence of extracellular Ca 2+ and was not blocked by indomethacin, suggesting that it is not mediated by production of prostaglandins. Since TGFα 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.
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