Studies on induction of delta-aminolevulinic acid synthase, ferrochelatase, cytochrome P-450 and cyclic AMP by phenformin. Chlorpropamide, allylisopropylacetamide and lead in hepatocytes from normal and experimental diabetic rats.
The present work demonstrates that phenformin exerted an inducing effect on delta-aminolevulinic acid synthase (ALA-S) and ferrochelatase activities and on cytochrome P-450 content in isolated hepatocytes from rats with experimental diabetes. Similar results were obtained with respect to ALA-S activity and cytochrome P-450 content when chlorpropamide was used. The inducing effect exerted by allylisopropylacetamide (AIA) on ALA-S and ferrochelatase activities in diabetic hepatic cells was markedly greater than that observed in normal hepatocytes. This stimulatory response was not enhanced by adding dibutyryl cyclic AMP (cAMP). When phenformin was added to isolated rat hepatocytes of normal rats, induction of ALA-S and ferrochelatase activities and cytochrome P-450 content was observed only in the presence of added dibutyryl cAMP. Addition of chlorpropamide to this in vitro system did not exert an inducing effect on the same enzymes even in the presence of dibutyryl cAMP. The present results add more experimental evidence about the lability of the heme pathway of diabetic hepatocytes.
Cánepa
E T
ET
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Llambías
E B
EB
Grinstein
M
M
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis*; D000502:Allylisopropylacetamide / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002747:Chlorpropamide / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005294:Ferrochelatase / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008190:Lyases / Q000096:biosynthesis*; D008297:Male; D010629:Phenformin / Q000494:pharmacology*; D051381:Rats
D000502:Allylisopropylacetamide; D007854:Lead; D003994:Bucladesine; D003577:Cytochrome P-450 Enzyme System; D010629:Phenformin; D000242:Cyclic AMP; D000624:5-Aminolevulinate Synthetase; D008190:Lyases; D005294:Ferrochelatase; D002747:Chlorpropamide