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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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0300483X_v290_n1_p22_Matkovic http://hdl.handle.net/20.500.12110/paper_0300483X_v290_n1_p22_Matkovic |
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paper:paper_0300483X_v290_n1_p22_Matkovic2023-06-08T15:27:18Z How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease Matkovic, Laura Beatriz San Martín de Viale, Leonor Carmen Mazzetti, Marta Blanca Acute porphyria model Glucocorticoids Glycogen phosphorylase Insulin Phosphoenolpyruvate carboxykinase UDP-glucuronosyltransferase 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester 5 aminolevulinate synthase allylisopropylacetamide carbohydrate corticosterone corticotropin glucocorticoid glucose glucuronosyltransferase glycogen phosphorylase insulin phosphoenolpyruvate carboxykinase (GTP) porphyrinogen pyruvate kinase acute intermittent porphyria animal experiment animal model article carbohydrate metabolism controlled study corticosterone release disease model enzyme activity female gluconeogenesis glucose metabolism glycogenolysis insulin blood level nonhuman priority journal rat Adrenocorticotropic Hormone Animals Corticosterone Disease Models, Animal Female Glucose Porphyria, Acute Intermittent Porphyrinogens Rats Rats, Wistar Rattus Rattus norvegicus 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. Fil:Matkovic, L.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:San Martín de Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Mazzetti, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0300483X_v290_n1_p22_Matkovic http://hdl.handle.net/20.500.12110/paper_0300483X_v290_n1_p22_Matkovic |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Acute porphyria model Glucocorticoids Glycogen phosphorylase Insulin Phosphoenolpyruvate carboxykinase UDP-glucuronosyltransferase 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester 5 aminolevulinate synthase allylisopropylacetamide carbohydrate corticosterone corticotropin glucocorticoid glucose glucuronosyltransferase glycogen phosphorylase insulin phosphoenolpyruvate carboxykinase (GTP) porphyrinogen pyruvate kinase acute intermittent porphyria animal experiment animal model article carbohydrate metabolism controlled study corticosterone release disease model enzyme activity female gluconeogenesis glucose metabolism glycogenolysis insulin blood level nonhuman priority journal rat Adrenocorticotropic Hormone Animals Corticosterone Disease Models, Animal Female Glucose Porphyria, Acute Intermittent Porphyrinogens Rats Rats, Wistar Rattus Rattus norvegicus |
| spellingShingle |
Acute porphyria model Glucocorticoids Glycogen phosphorylase Insulin Phosphoenolpyruvate carboxykinase UDP-glucuronosyltransferase 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester 5 aminolevulinate synthase allylisopropylacetamide carbohydrate corticosterone corticotropin glucocorticoid glucose glucuronosyltransferase glycogen phosphorylase insulin phosphoenolpyruvate carboxykinase (GTP) porphyrinogen pyruvate kinase acute intermittent porphyria animal experiment animal model article carbohydrate metabolism controlled study corticosterone release disease model enzyme activity female gluconeogenesis glucose metabolism glycogenolysis insulin blood level nonhuman priority journal rat Adrenocorticotropic Hormone Animals Corticosterone Disease Models, Animal Female Glucose Porphyria, Acute Intermittent Porphyrinogens Rats Rats, Wistar Rattus Rattus norvegicus Matkovic, Laura Beatriz San Martín de Viale, Leonor Carmen Mazzetti, Marta Blanca How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease |
| topic_facet |
Acute porphyria model Glucocorticoids Glycogen phosphorylase Insulin Phosphoenolpyruvate carboxykinase UDP-glucuronosyltransferase 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinedicarboxylic acid diethyl ester 5 aminolevulinate synthase allylisopropylacetamide carbohydrate corticosterone corticotropin glucocorticoid glucose glucuronosyltransferase glycogen phosphorylase insulin phosphoenolpyruvate carboxykinase (GTP) porphyrinogen pyruvate kinase acute intermittent porphyria animal experiment animal model article carbohydrate metabolism controlled study corticosterone release disease model enzyme activity female gluconeogenesis glucose metabolism glycogenolysis insulin blood level nonhuman priority journal rat Adrenocorticotropic Hormone Animals Corticosterone Disease Models, Animal Female Glucose Porphyria, Acute Intermittent Porphyrinogens Rats Rats, Wistar Rattus Rattus norvegicus |
| description |
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. |
| author |
Matkovic, Laura Beatriz San Martín de Viale, Leonor Carmen Mazzetti, Marta Blanca |
| author_facet |
Matkovic, Laura Beatriz San Martín de Viale, Leonor Carmen Mazzetti, Marta Blanca |
| author_sort |
Matkovic, Laura Beatriz |
| title |
How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease |
| title_short |
How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease |
| title_full |
How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease |
| title_fullStr |
How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease |
| title_full_unstemmed |
How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease |
| title_sort |
how porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. their relevance in the onset of this disease |
| publishDate |
2011 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0300483X_v290_n1_p22_Matkovic http://hdl.handle.net/20.500.12110/paper_0300483X_v290_n1_p22_Matkovic |
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