Effect of Astragaloside IV on Hepatic Glucose-regulating Enzymes in Diabetic Mice Induced by a High-fat Diet and Streptozotocin

Aim: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) are important in control of blood glucose homeostasis, and are considered to he potential targets for antidiabetic drugs. Astragaloside IV has been reported to have a hypoglycemic effect. However, the biochemical mechanisms by which astragaloside IV regulates hepatic glucose-metabolizing enzymes remain unknown. The present study examines whether GP and G6Pase mediate the hypoglycemic effect of astragaloside IV. Methods: Type 2 diabetic mice were treated with astragaloside IV for 2 weeks. Blood glucose and insulin levels were measured by a glucometer and the ELISA method, respectively. Total cholesterol (TC) and triglyceride (TG) levels were determined using Labassay (TM) kits. Activities of hepatic GP and G6Pase were measured by the glucose-6-phosphate dehydrogenase-coupled reaction. The mRNA and protein levels of both enzymes were determined by real-time RT-PCR and Western blotting. Results: Astragaloside IV at 25 and 50 mg/kg significally decreased the blood glucose, TG and insulin levels, and inhibited the mRNA and protein expression as well as enzyme activity of GP and G6Pase in diabetic mice. Conclusions: Astragaloside IV exhibited a hypoglycemic effect in diabetic mice. The hypoglycemic effect of this compound may be explained, in part, by its inhibition of hepatic CP and G6Pase activities. Copyright (C) 2009 John Wiley & Sons, Ltd.