In vitro inhibition of human erythrocyte hexokinase by various hyperglycemic drugs

Abstract

Hemolysis is the red blood cell abnormality most often associated with adverse effect of drug therapy. Drug-induced or drug-associated hyperglycemia could decrease the activity of hexokinase. The aim of this study was to investigate the inhibitory effects of some commonly used drugs that have hyperglycemic side effect on the human erythrocyte hexokinase enzyme in vitro. Hexokinase was purified from human erythrocytes using sequential chromatography, with a specific activity of 0.96 ± 0.18 U/g hemoglobin, and assayed in the presence of selected drugs that have hyperglycemic side effect. The IC were determined from the regression analysis graph. Correlation analysis showed that there was positive correlation between the hyperglycemic side effect of some of the tested drugs and decrease of hexokinase activity. This suggests that, at least in part, these drugs exert their hyperglycemic effect by inhibiting glucose phosphorylation by the hexokinase, which consequently causes the glucose accumulation.

Evaluation of the Antidiabetic Potential of Extracts of Urtica dioica, Apium graveolens, and Zingiber officinale in Mice, Zebrafish, and Pancreatic β-Cell

“…The level of G6P is determined by phosphofructokinase, which is connected to the G6P isomerase reaction operating at quasi-equilibrium. An increase in the phosphofructokinase activity can reduce G6P; therefore, hexokinase transforms are disinhibited, which consequently increases glucose utilization [ 33 ].…”

“…Therefore, the achievement of good glycemic control is essential to prevent or delay diabetes complications. Herein, diabetic mice treated with UAZ showed a significant reduction in blood glucose levels increasing peripheral glucose utilization and decrease hepatic gluconeogenesis supported by increase the activity of hepatic glycolytic enzymes, such as hexokinase, phosphofructokinase, fructose-1, 6-bisphosphatase, glucose-6-phosphatase, and glucose-6-phosphatase dehydrogenase in the liver suggest that the hypoglycemic effect in part might be due to increased peripheral glucose utilization and decreased gluco-neogenesis in the liver through its insulin mimetic effect [ 33 ].…”