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Abstract:

11 beta-hydroxysteroid dehydrogenase (HSDs) enzymes regulate the activity of glucocorticoids in target organs. HSD1, one of the two existing isoforms, locates mainly in CNS, liver and adipose tissue. HSD1 is involved in the pathogenesis of diseases such as obesity, insulin resistance, arterial hypertension and the Metabolic Syndrome. The stress produced by HC1 overload triggers metabolic acidosis and increases liver HSD1 activity associated with increased phosphoenolpyruvate carboxykinase, a regulatory enzyme of gluconeogenesis that is activated by glucocorticoids, with increased glycaemia and glycogen breakdown. The aim of this study was to analyze whether the metabolic modifications triggered by HC1 stress are due to increased liver HSD1 activity. Glycyrrhetinic acid, a potent HDS inhibitor, was administered subcutaneously (20 mg/ml) to stressed and unstressed four months old male Sprague Dawley rats to investigate changes in liver HSD1, phosphoenolpyruvate carboxykinase (PECPK) and glycogen phosphorylase activities and plasma glucose levels. It was observed that all these parameters increased in stressed animals, but that treatment with glycyrrhetinic acid significantly reduced their levels. In conclusion, our results demonstrate the involvement of HSD1 in stress induced carbohydrate disturbances and could contribute to the impact of HSD1 inhibitors on carbohydrate metabolism and its relevance in the study of Metabolic Syndrome Disorder and non insulin-dependent diabetes mellitus.

Registro:

Documento: Artículo
Título:Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat
Autor:Altuna, M.E.; Mazzetti, M.B.; Rago, L.F.; De Viale, L.C.S.M.; Damasco, M.C.
Filiación:Laboratorio de Fisiología Endocrina, Consejo Nacional de Investigaciones Científicas, Técnicas (CONICET), Venezuela
Laboratorio de Disturbios Metabólicos por Xenobióticos, Departamento de Quimica Biológica, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Palabras clave:Glucose; Glycyrrhetinic acid; HSD1; Pepck; Stress; 11beta hydroxysteroid dehydrogenase 1; carbohydrate; chloride; glucose; glycogen phosphorylase; glycyrrhetinic acid; phosphoenolpyruvate carboxykinase (ATP); acidity; animal experiment; animal tissue; article; carbohydrate metabolism; controlled study; enzyme activity; glucose blood level; glucose metabolism; male; metabolic syndrome X; non insulin dependent diabetes mellitus; nonhuman; rat; 11-beta-Hydroxysteroid Dehydrogenases; Adipose Tissue; Animals; Carbohydrate Metabolism; Carbohydrates; Central Nervous System; Glucose; Glycyrrhetinic Acid; Liver; Male; Models, Biological; Phosphoenolpyruvate Carboxykinase (ATP); Protein Isoforms; Rats; Rats, Sprague-Dawley; Animalia; Rattus
Año:2009
Volumen:65
Número:4
Página de inicio:329
Página de fin:337
DOI: http://dx.doi.org/10.1007/BF03185927
Título revista:Journal of Physiology and Biochemistry
Título revista abreviado:J. Physiol. Biochem.
ISSN:11387548
CODEN:JPBIF
CAS:chloride, 16887-00-6; glucose, 50-99-7, 84778-64-3; glycogen phosphorylase, 9032-10-4; glycyrrhetinic acid, 471-53-4; phosphoenolpyruvate carboxykinase (ATP), 9073-94-3; 11-beta-Hydroxysteroid Dehydrogenases, 1.1.1.146; Carbohydrates; Glucose, 50-99-7; Glycyrrhetinic Acid, 471-53-4; Phosphoenolpyruvate Carboxykinase (ATP), 4.1.1.49; Protein Isoforms
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_11387548_v65_n4_p329_Altuna

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Citas:

---------- APA ----------
Altuna, M.E., Mazzetti, M.B., Rago, L.F., De Viale, L.C.S.M. & Damasco, M.C. (2009) . Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat. Journal of Physiology and Biochemistry, 65(4), 329-337.
http://dx.doi.org/10.1007/BF03185927
---------- CHICAGO ----------
Altuna, M.E., Mazzetti, M.B., Rago, L.F., De Viale, L.C.S.M., Damasco, M.C. "Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat" . Journal of Physiology and Biochemistry 65, no. 4 (2009) : 329-337.
http://dx.doi.org/10.1007/BF03185927
---------- MLA ----------
Altuna, M.E., Mazzetti, M.B., Rago, L.F., De Viale, L.C.S.M., Damasco, M.C. "Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat" . Journal of Physiology and Biochemistry, vol. 65, no. 4, 2009, pp. 329-337.
http://dx.doi.org/10.1007/BF03185927
---------- VANCOUVER ----------
Altuna, M.E., Mazzetti, M.B., Rago, L.F., De Viale, L.C.S.M., Damasco, M.C. Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat. J. Physiol. Biochem. 2009;65(4):329-337.
http://dx.doi.org/10.1007/BF03185927