How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease
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. Female Wistar rats were treated...
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2011
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| LEADER | 16264caa a22014777a 4500 | ||
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| 003 | AR-BaUEN | ||
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| 024 | 7 | |2 cas |a 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester, 12772-36-0, 632-93-9; 5 aminolevulinate synthase, 9037-14-3; allylisopropylacetamide, 299-78-5; corticosterone, 50-22-6; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; glucose, 50-99-7, 84778-64-3; glucuronosyltransferase, 37329-64-9, 9030-08-4; glycogen phosphorylase, 9032-10-4; insulin, 9004-10-8; phosphoenolpyruvate carboxykinase (GTP), 9013-08-5; porphyrinogen, 4396-11-6; pyruvate kinase, 9001-59-6; Adrenocorticotropic Hormone, 9002-60-2; Corticosterone, 50-22-6; Glucose, 50-99-7; Porphyrinogens | |
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| 100 | 1 | |a Matkovic, L.B. | |
| 245 | 1 | 4 | |a How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease |
| 260 | |c 2011 | ||
| 270 | 1 | 0 | |m Mazzetti, M.B.; Laboratorio de Disturbios Metabólicos por Xenobióticos, Salud Humana y Medio Ambiente, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, 4to Piso, C1428EGA Ciudad Autónoma de Buenos Aires, Argentina; email: mazzetti@qb.fcen.uba.ar |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a 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. Female Wistar rats were treated with 2-allyl-2-isopropylacetamide (AIA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) using different doses of AIA (100, 250 and 500 mg/kg body weight) and a single dose of DDC (50 mg DDC/kg body weight). Rats were sacrificed 16 h after AIA/DDC administration. In the group treated with the highest dose of AIA (group H), hepatic 5-aminolevulinic acid synthase (ALA-S) increased more than 300%, phosphoenolpyruvate carboxykinase (PEPCK) and glycogen phosphorylase (GP) activities were 43% and 46% lower than the controls, respectively, plasmatic insulin levels exceeded normal values by 617%, and plasmatic glucocorticoids (GC) decreased 20%. GC results are related to a decrease in corticosterone (CORT) adrenal production (33%) and a significant reduction in its metabolization by UDP-glucuronosyltransferase (UGT) (62%). Adrenocorticotropic hormone (ACTH) stimulated adrenal production 3-fold and drugs did not alter this process. 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. © 2011 Elsevier Ireland Ltd. |l eng | |
| 536 | |a Detalles de la financiación: Universidad de Buenos Aires, UBACyT | ||
| 536 | |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas | ||
| 536 | |a Detalles de la financiación: We thank María Croce and Mariana Casalía for their technical assistance. This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and the Universidad de Buenos Aires (UBACyT) . L.C. San Martín de Viale is a Scientific Research Career Member of CONICET. | ||
| 593 | |a Laboratorio de Disturbios Metabólicos por Xenobióticos, Salud Humana y Medio Ambiente, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, 4to Piso, C1428EGA Ciudad Autónoma de Buenos Aires, Argentina | ||
| 690 | 1 | 0 | |a ACUTE PORPHYRIA MODEL |
| 690 | 1 | 0 | |a GLUCOCORTICOIDS |
| 690 | 1 | 0 | |a GLYCOGEN PHOSPHORYLASE |
| 690 | 1 | 0 | |a INSULIN |
| 690 | 1 | 0 | |a PHOSPHOENOLPYRUVATE CARBOXYKINASE |
| 690 | 1 | 0 | |a UDP-GLUCURONOSYLTRANSFERASE |
| 690 | 1 | 0 | |a 1,4 DIHYDRO 2,4,6 TRIMETHYL 3,5 PYRIDINEDICARBOXYLIC ACID DIETHYL ESTER |
| 690 | 1 | 0 | |a 5 AMINOLEVULINATE SYNTHASE |
| 690 | 1 | 0 | |a ALLYLISOPROPYLACETAMIDE |
| 690 | 1 | 0 | |a CARBOHYDRATE |
| 690 | 1 | 0 | |a CORTICOSTERONE |
| 690 | 1 | 0 | |a CORTICOTROPIN |
| 690 | 1 | 0 | |a GLUCOCORTICOID |
| 690 | 1 | 0 | |a GLUCOSE |
| 690 | 1 | 0 | |a GLUCURONOSYLTRANSFERASE |
| 690 | 1 | 0 | |a GLYCOGEN PHOSPHORYLASE |
| 690 | 1 | 0 | |a INSULIN |
| 690 | 1 | 0 | |a PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP) |
| 690 | 1 | 0 | |a PORPHYRINOGEN |
| 690 | 1 | 0 | |a PYRUVATE KINASE |
| 690 | 1 | 0 | |a ACUTE INTERMITTENT PORPHYRIA |
| 690 | 1 | 0 | |a ANIMAL EXPERIMENT |
| 690 | 1 | 0 | |a ANIMAL MODEL |
| 690 | 1 | 0 | |a ARTICLE |
| 690 | 1 | 0 | |a CARBOHYDRATE METABOLISM |
| 690 | 1 | 0 | |a CONTROLLED STUDY |
| 690 | 1 | 0 | |a CORTICOSTERONE RELEASE |
| 690 | 1 | 0 | |a DISEASE MODEL |
| 690 | 1 | 0 | |a ENZYME ACTIVITY |
| 690 | 1 | 0 | |a FEMALE |
| 690 | 1 | 0 | |a GLUCOSE METABOLISM |
| 690 | 1 | 0 | |a GLYCOGENOLYSIS |
| 690 | 1 | 0 | |a INSULIN BLOOD LEVEL |
| 690 | 1 | 0 | |a NONHUMAN |
| 690 | 1 | 0 | |a PRIORITY JOURNAL |
| 690 | 1 | 0 | |a RAT |
| 690 | 1 | 0 | |a ADRENOCORTICOTROPIC HORMONE |
| 690 | 1 | 0 | |a ANIMALS |
| 690 | 1 | 0 | |a CORTICOSTERONE |
| 690 | 1 | 0 | |a DISEASE MODELS, ANIMAL |
| 690 | 1 | 0 | |a FEMALE |
| 690 | 1 | 0 | |a GLUCOSE |
| 690 | 1 | 0 | |a PORPHYRIA, ACUTE INTERMITTENT |
| 690 | 1 | 0 | |a PORPHYRINOGENS |
| 690 | 1 | 0 | |a RATS |
| 690 | 1 | 0 | |a RATS, WISTAR |
| 690 | 1 | 0 | |a RATTUS |
| 690 | 1 | 0 | |a RATTUS NORVEGICUS |
| 650 | 1 | 7 | |2 spines |a GLUCONEOGENESIS |
| 700 | 1 | |a D'Andrea, F. | |
| 700 | 1 | |a Fornes, D. | |
| 700 | 1 | |a San Martín de Viale, L.C. | |
| 700 | 1 | |a Mazzetti, M.B. | |
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