GLIQUIDONE INFLUENCE ON THE P-GLYCOPROTEIN EXPRESSION ON THE BACKGROUND OF NORM AND EXPERIMENTAL ALLOXAN-INDUCED DIABETES MELLITUS TYPE 2

In recent years in the pharmacokinetics of drugs more and more importance is attached to proteins-transporters, most clinically significant of which is the P-glycoprotein (P-gp, ABCB1 protein, MDR1), due to its broad substrate specificity and localization in the body. In in vivo study at intact rabbits and rabbits with experimental alloxan-induced diabetes mellitus (DM) type 2 the effect of gliquidone on P-gp expression in jejunum, liver, kidney and blood-brain barrier was investigated by indirect immunohistochemistry method. Gliquidone administration (10 mg/kg) did not lead to changes of P-gp expression at intact rabbits, however, was accompanied by a decrease in the level of fasting blood glucose – endogenous inhibitor of the ABCB1 protein. These results were maintained on the 5th day of drug withdrawal. 14-days gliquidone therapy (10 mg/kg) of alloxan-induced diabetes type 2 showed restoring expression of ABCB1 protein in jejunum, liver and kidney reduced on the pathology background to the level of intact rabbits, while there was normalization of carbohydrate metabolism. On the 5th day of gliquidone withdrawal inhibition of P-gp expression was occurred again in jejunum and liver. It is likely that the observed decrease in the P-gp expression on a background of diabetes type 2 was associated with an increase glucose levels in blood and decrease insulin concentration – endogenous inducer of transporter protein. In the therapy by gliquidone normalization of carbohydrate metabolism and as a consequence restoring of declined on the background of the pathology ABCB1 protein expression were observed. On the 5th day of gliquidone withdrawal increase in blood glucose level and decrease insulin concentration were observed. In the result reduction of the level of P-gp expression in the tissues of jejunum and liver, and a tendency to decrease in the kidneys were observed again.