Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from normal and experimental-diabetic rats. Role of insulin.
In the present work we demonstrate that insulin decreases the phenobarbital-induced activities of delta-aminolevulinic acid synthase and ferrochelatase in isolated hepatocytes from normal and experimental-diabetic rats. Insulin concentrations required to produce significant inhibition in diabetic hepatocytes were higher than in normal cells. Under similar experimental conditions, insulin decreased the basal activities of delta-aminolevulinic acid synthase and ferrochelatase in hepatocytes from normal rats; no inhibitory effect was observed on the basal activity of delta-aminolevulinic acid synthase in hepatocytes from diabetic rats. Cytochrome P-450 content of both normal and diabetic cells was not affected by insulin in absence or presence of phenobarbital. The inhibitory action of insulin was exerted even when effective concentrations of glucagon, dexamethasone, or 8-(p-chlorophenylthio)-cAMP were present.
Cánepa
E T
ET
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.
Llambías
E B
EB
Grinstein
M
M
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005294:Ferrochelatase / Q000378:metabolism; D005934:Glucagon / Q000502:physiology; D006418:Heme / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D007328:Insulin; D006418:Heme; D003907:Dexamethasone; D005934:Glucagon; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D000624:5-Aminolevulinate Synthetase; D005294:Ferrochelatase; D010634:Phenobarbital