EXPRESSION AND ACTIVITY OF AMINOTRANSFERASES IN THE LIVER OF STREPTOZOTOCIN-DIABETIC RATS: THE EFFECT OF MIFEPRISTONE.

Context: Interventions that suppress hepatic gluconeogenesis from amino acids may be useful for improving glycemic control in diabetic patients.

Objectives: It was shown that administration of glucocorticoid receptor antagonist Mifepristone (MIF) leads to variously pronounced changes in the alanine-, aspartate-, tyrosine- aminotransferases (ALT, AST, TAT) activity in the liver of experimental animals. It has been suggested that this selective effect of MIF may be related to differences in the expression of the corresponding genes.

Effects Mifepristone on Aminotransferase Activities in the Liver in Rats with Streptozotocin-Induced Diabetes Mellitus.

The glucocorticoid status and activities of ALT, AST, and tyrosine aminotransferase in the liver are studied in rats with streptozotocin-induced diabetes mellitus in response to repeated intraperitoneal injections of mifepristone. Diabetic rats develop an increase of the blood corticosterone and liver aminotransferase levels in response to mifepristone. These results indicate that in diabetic animals the glucocorticoid hormones with high blood concentrations, increasing still more in response to mifepristone, overcome the receptor blockade, and realize their regulatory functions in hepatocytes.

Stress Response to Physical Exercise in Rats with Alimentary Obesity.

Stress response to physical exercise was studied in rats with alimentary obesity with and without caloric diet restriction. Daily excretion of corticosterone, progesterone, and testosterone, weights of internal organs, and serum levels of glucose, free fatty acids, triglycerides, corticosterone, and testosterone were estimated. Stress response to moderate exercise in rats with alimentary obesity was associated with predominance of anabolic influence of testosterone over the catabolic effects of corticosterone, which promoted the increase in the weight of reproductive organs.

Effect of Mifepristone on Corticosteroid Production in Vitro by Adrenal Glands of Rats with Streptozotocin Diabetes.

Changes in pregnenolone and corticosterone production by the adrenal glands of normoglycemic rats receiving the course of intraperitoneal mifepristone or NaCl administration were co-directed, but differed in magnitude. In rats with hyperglycemia, corticosteroid production increased after NaCl administration over 5 days and returned to the initial values after 15-day administration. On the contrary, pregnenolone and corticosterone production was suppressed after 5-day course of mifepristone, but significantly increased after mifepristone administration for 15 days.

Effects of Intraperitoneal Administration of Mifepristone on Glucocorticoid Status of Experimental Animals.

We studied the content of corticosterone and its precursors in the adrenal glands, corticosterone in blood serum and daily urine of rats, and activity of first and second isoforms of 11β-hydroxysteroid dehydrogenase in the liver and kidneys of rats after 15 daily intraperitoneal injections of 0.9% NaCl or glucocorticoid receptor blocker mifepristone in 0.9% NaCl.