Induction of delta-aminolevulinate synthase and cytochrome P-450 hemoproteins in hepatocyte culture. Effect of glucose and hormones.

摘要: Addition of glucose to cultured chick embryo hepatocytes caused a concentration-dependent impairment phenobarbital-mediated induction delta-aminolevulinate (ALA) synthase resembling the "glucose effect" observed in rodents vivo. This effect occurred complete absence extrahepatic factors such as serum and hormones. Fructose, glycerol, lactate mimicked inhibitory on ALA induction, whereas 2-deoxyglucose 3-O-methylglucose augmented evoked by phenobarbital. 2-Deoxyglucose reversed glucose, suggesting that is mediated free or 6-phosphate nonglycolytic metabolite 6-phosphate. The cytochrome P-450 hemoprotein(s) its monooxygenase function were concomitantly diminished glucose. However, this was reversible addition exogenous heme primary target not synthesis apocytochrome P-450. Glucagon dibutyryl cAMP enhanced phenobarbital partially counteracted both enzymes may be changes levels. Although insulin did alter synthase, it impaired even presence glucagon cAMP. These data relevant for treatment with patients "inducible" hepatic porphyria.