V G Selyatitskaya 1 , N Palchikova 1 , A Tsidulko 1 , O I Kuzminova 1 Show Affiliations »
Abstract
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. The aim of the study was to investigate the gene expression and activity of ALT, AST and TAT in the liver of rats with streptozotocin-related diabetes (StD) under the long-term oral MIF administration. Methods: Male Wistar rats (n=48) with StD under the 10-days oral MIF administration were used. It was measured the activity of ALT, AST, TAT enzymes and relative expression of this genes in the liver of experimental animals. Results: In rats with StD the gene expression of all three studied aminotransferases in the liver was statistically significantly increased and their activity was increased as well. MIF administration did not change the studied genes expression and enzymes activity to healthy rats and caused a decrease in expression of ALT and AST genes and activity of these enzymes to rats with StD. However, the expression of the TAT gene and the activity of this enzyme in the liver of rats with StD increased upon MIF administration in comparison with animals with StD. Conclusions: The introduction of MIF against the background of StD reduces the expression of genes and the activity of ALT and AST in the liver, what determine the transamination of amino acids to include them in gluconeogenesis, but increases the expression of genes and the activity of TAT, what determine the inclusion of tyrosine in the biogenic amines synthesis. The mechanisms of such selectivity require further study. ©2022 Acta Endocrinologica (Buc).
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. The aim of the study was to investigate the gene expression and activity of ALT, AST and TAT in the liver of rats with streptozotocin-related diabetes (StD) under the long-term oral MIF administration. Methods: Male Wistar rats (n=48) with StD under the 10-days oral MIF administration were used. It was measured the activity of ALT, AST, TAT enzymes and relative expression of this genes in the liver of experimental animals. Results: In rats with StD the gene expression of all three studied aminotransferases in the liver was statistically significantly increased and their activity was increased as well. MIF administration did not change the studied genes expression and enzymes activity to healthy rats and caused a decrease in expression of ALT and AST genes and activity of these enzymes to rats with StD. However, the expression of the TAT gene and the activity of this enzyme in the liver of rats with StD increased upon MIF administration in comparison with animals with StD. Conclusions: The introduction of MIF against the background of StD reduces the expression of genes and the activity of ALT and AST in the liver, what determine the transamination of amino acids to include them in gluconeogenesis, but increases the expression of genes and the activity of TAT, what determine the inclusion of tyrosine in the biogenic amines synthesis. The mechanisms of such selectivity require further study. ©2022 Acta Endocrinologica (Buc).
Entities: Chemical
Keywords:
aminotransferase gene expression; enzyme activity; liver; mifepristone; rats; streptozotocin diabetes
Year: 2022
PMID： 36212251 PMCID： PMC9512388 DOI： 10.4183/aeb.2022.145
Source DB: PubMed Journal: Acta Endocrinol (Buchar) ISSN： 1841-0987 Impact factor: 1.104