Effect of stress on hepatic 11beta-hydroxysteroid dehydrogenase activity and its influence on carbohydrate metabolism.
Stress activates the synthesis and secretion of catecholamines and adrenal glucocorticoids, increasing their circulating levels. In vivo, hepatic 11beta-hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11-dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at tissue level. We studied the effect of 3 types of stress, 1 induced by bucogastric overload with 200 mmol/L HCl causing metabolic acidosis (HCl), the second induced by bucogastric overload with 0.45% NaCl (NaCl), and the third induced by simulated overload (cannula), on the kinetics of hepatic HSD1 of rats and their influence on the activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, glycemia, and glycogen deposition. Compared with unstressed controls, all types of stress significantly increased HSD1 activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29% cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68% NaCl, and 78% HCl). Owing to these results, we suggest the following events occur when stress is induced: an increase in hepatic HSD1 activity, augmented active glucocorticoid levels, increased gluconeogenesis, and glycemia. Also involved are the multiple events indirectly related to glucocorticoids, which lead to the depletion of hepatic glycogen deposits, thereby contributing to increased glycemia. This new approach shows that stress increments the activity of hepatic HSD1 and suggests that this enzyme could be involved in the development of the Metabolic Syndrome.
Altuna
María Eugenia
ME
Laboratorio de Esteroides, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Química Biológica Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina.
Lelli
Sandra Marcela
SM
San Martín de Viale
Leonor C
LC
Damasco
María Cristina
MC
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000201:enzymology*
D001786:Blood Glucose; D008112:Liver Glycogen; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D042842:11-beta-Hydroxysteroid Dehydrogenases; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D003345:Corticosterone