Selyatitskaya V G, Palchikova N, Tsidulko A, Kuzminova O I
FSBSI Federal Research Center of Fundamental and Translational Medicine Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
Acta Endocrinol (Buchar). 2022 Apr-Jun;18(2):145-149. doi: 10.4183/aeb.2022.145.
Interventions that suppress hepatic gluconeogenesis from amino acids may be useful for improving glycemic control in diabetic patients.
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.
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.
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.
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.
抑制肝脏从氨基酸进行糖异生的干预措施可能有助于改善糖尿病患者的血糖控制。
已表明给予糖皮质激素受体拮抗剂米非司酮（MIF）会导致实验动物肝脏中丙氨酸转氨酶、天冬氨酸转氨酶、酪氨酸转氨酶（ALT、AST、TAT）活性发生不同程度的显著变化。有人认为MIF的这种选择性作用可能与相应基因表达的差异有关。本研究的目的是调查长期口服MIF的链脲佐菌素诱导糖尿病（StD）大鼠肝脏中ALT、AST和TAT的基因表达及活性。
使用雄性Wistar大鼠（n = 48），给予其10天口服MIF以诱导StD。测定实验动物肝脏中ALT、AST、TAT酶的活性以及这些基因的相对表达。
在StD大鼠中，肝脏中所有三种研究的转氨酶的基因表达在统计学上显著增加，其活性也增加。给予MIF对健康大鼠的研究基因表达和酶活性没有影响，而对StD大鼠则导致ALT和AST基因表达及这些酶活性降低。然而，与StD大鼠相比，给予MIF后StD大鼠肝脏中TAT基因的表达和该酶的活性增加。
在StD背景下引入MIF可降低肝脏中ALT和AST的基因表达及活性，ALT和AST决定氨基酸转氨作用以将其纳入糖异生过程，但会增加TAT的基因表达和活性，TAT决定酪氨酸纳入生物胺合成过程。这种选择性的机制需要进一步研究。
