Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from experimental-diabetic rats

• Published in: Biochimica et biophysica acta Vol. 847; no. 2; pp. 191 - 197
• Main Authors: Cánepa, Eduardo T., Galvagno, Miguel A., Llambías, Elena B.C., Passeron, Susana, Grinstein, Moisés
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20.11.1985; Elsevier; North-Holland
• Subjects: 5-Aminolevulinate Synthetase - metabolism; Animals; Biological and medical sciences; Bucladesine - pharmacology; cyclic AMP; Cyclic AMP - metabolism; Cytochrome P-450; Cytochrome P-450 Enzyme System - metabolism; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Diabetic rat hepatocyte; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme induction; Ferrochelatase; Ferrochelatase - metabolism; Glucose - pharmacology; Heme - biosynthesis; Homeostasis; In Vitro Techniques; Kinetics; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Phenobarbital - pharmacology; Rats; Rats, Inbred Strains; Reference Values; δ-Aminolevulinic acid synthase; cyclic AMP; Diabetic rat hepatocyte; Ferrochelatase; Enzyme induction; Cytochrome P-450; δ-Aminolevulinic acid synthase; Endocrinopathy; Animal model; Vertebrata; Mammalia; Hepatocyte; Rat; Diabetes mellitus; Rodentia; Heme; Biosynthesis
• ISSN: 0167-4889; 0006-3002; 1879-2596; 1878-2434
• DOI: 10.1016/0167-4889(85)90020-5

Isolated hepatocytes from rats with experimental diabetes exhibit increased content of cytochrome P-450 and cyclic AMP and normal activities of the regulatory enzymes δ-aminolevulinic acid synthase and ferrochelatase. The inducing effect exerted by phenobarbital on cytochrome P-450, δ-aminolevulinic acid synthase and ferrochelatase biosynthesis and cyclic AMP content in diabetic hepatic cells is markedly greater than that observed in normal hepatocytes. This stimulatory response is neither enhanced by added dibutyryl cyclic AMP nor repressed by glucose. The present results suggest that the heme pathway of diabetic hepatocytes is more susceptible to porphyrinogenic factors.