Glucose inhibits phenobarbital-induced δ-aminolevulinate synthase expression in normal but not in diabetic rat hepatocytes

Author:

Varone Cecilia L.,Cánepa Eduardo T.,Llambías Elena B. C.,Grinstein Moisés

Abstract

In the present work, we demonstrate the presence of a glucose inhibitory effect on the phenobarbital-mediated induction of the δ-aminolevulinate synthase mRNA in normal rat hepatocytes, consistent with the results obtained with the δ-aminolevulinate synthase activity previously reported. This "glucose effect" can be prevented by adding cAMP, adenylate cyclase activators, or a phosphodiesterase inhibitor. δ-Aminolevulinate synthase mRNA half-life is not modified in the presence of phenobarbital or glucose. When the same experiments are performed using diabetic cells, no glucose effect is observed, even when the endogenous cAMP content is lowered to normal levels. The results obtained in this study suggest that glucose decreases δ-aminolevulinate synthase biosynthesis by acting at a pretranslational step. Assuming that the glucose effect operates by a repression mechanism exerted by metabolites derived from or related to glucose, the present results may reflect a derangement in the formation of these metabolites as a result of the abnormal metabolism operating in the diabetic state.Key words: glucose, δ-aminolevulinate synthase expression, diabetic rat hepatocytes, phenobarbital, cAMP.

Publisher

Canadian Science Publishing

Subject

Cell Biology,Molecular Biology,Biochemistry

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