Porphyrinogenic drugs, acute porphyria, hormonal status and glucose metabolism

A PubMed study by Matkovic LB1, D’Andrea F, Fornes D, San Martín de Viale LC, Mazzetti MB.

Abstract

This work deals with the study of how porphyrinogenic drugs modeling acute porphyrias interfere with the status of carbohydrate-regulating hormones in relation to key glucose enzymes and to porphyria, considering that glucose modulates the development of the disease. … Thus, porphyria-inducing drugs AIA and DDC dramatically altered the status of hormones that regulate carbohydrate metabolism increasing insulin levels and reducing GC production, metabolization and plasmatic levels.

In this acute porphyria model, gluconeogenic and glycogenolytic blockages caused by PEPCK and GP depressed activities, respectively, would be mainly a consequence of the negative regulatory action of insulin on these enzymes. GC could also contribute to PEPCK blockage both because they were depressed by the treatment and because they are positive effectors on PEPCK. These disturbances in carbohydrates and their regulation, through ALA-S de-repression, would enhance the porphyria state promoted by the drugs on heme synthesis and destruction. This might be the mechanism underlying the “glucose effect” observed in hepatic porphyrias. The statistical correlation study performed showed association between all the variables studied and reinforce these conclusions.

 

PMID: 21889565   DOI: 10.1016/j.tox.2011.08.014   Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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