Effect of geniposide, a hypoglycemic glucoside, on hepatic regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin  

作　　者：Shao-yu WU Guang-fa WANG Zhong-qiu LIU in-jun RAO Lin Lü Wei XU Shu-guang WU Jia-jie ZHANG 

机构地区：[1]School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China

出　　处：《Acta Pharmacologica Sinica》2009年第2期202-208,共7页中国药理学报（英文版）

摘　　要：Aim： Hepatic glycogen phosphorylase （GP） and glucose-6-phosphatase （G6Pase） play an important role in the control of blood glucose homeostasis and are proposed to be potential targets for anti-diabetic drugs. Geniposide is an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits and has been reported to have a hypoglycemic effect. However, little is known about the biochemical mechanisms by which geniposide regulates hepatic glucose-metabolizing enzymes. The present study investigates whether the hypoglycemic effect of geniposide is mediated by GP or G6Pase. Methods： Type 2 diabetic mice, induced by a high-fat diet and streptozotocin injection, were treated with or without geniposide for 2 weeks. Blood glucose levels were monitored by a glucometer. Insulin concentrations were analyzed by the ELISA method. Total cholesterol （TC） and triglyceride （TG） levels were measured using LabassayTM kits. Activities of hepatic GP and G6Pase were measured by glucose-6-phosphate dehydrogenase-coupled reaction. Real-time RT-PCR and Western blotting were used to determine the mRNA and protein levels of both enzymes. Results： Geniposide （200 and 400 mg/kg） significantly decreased the blood glucose, insulin and TG levels in diabetic mice in a dose-dependent manner. This compound also decreased the expression of GP and G6Pase at mRNA and immunoreactive protein levels, as well as enzyme activity. Conclusion： Geniposide is an effective hypoglycemic agent in diabetic mice. The hypoglycemic effect of this compound may be mediated, at least in part, by inhibiting the GP and G6Pase activities.Aim： Hepatic glycogen phosphorylase （GP） and glucose-6-phosphatase （G6Pase） play an important role in the control of blood glucose homeostasis and are proposed to be potential targets for anti-diabetic drugs. Geniposide is an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits and has been reported to have a hypoglycemic effect. However, little is known about the biochemical mechanisms by which geniposide regulates hepatic glucose-metabolizing enzymes. The present study investigates whether the hypoglycemic effect of geniposide is mediated by GP or G6Pase. Methods： Type 2 diabetic mice, induced by a high-fat diet and streptozotocin injection, were treated with or without geniposide for 2 weeks. Blood glucose levels were monitored by a glucometer. Insulin concentrations were analyzed by the ELISA method. Total cholesterol （TC） and triglyceride （TG） levels were measured using LabassayTM kits. Activities of hepatic GP and G6Pase were measured by glucose-6-phosphate dehydrogenase-coupled reaction. Real-time RT-PCR and Western blotting were used to determine the mRNA and protein levels of both enzymes. Results： Geniposide （200 and 400 mg/kg） significantly decreased the blood glucose, insulin and TG levels in diabetic mice in a dose-dependent manner. This compound also decreased the expression of GP and G6Pase at mRNA and immunoreactive protein levels, as well as enzyme activity. Conclusion： Geniposide is an effective hypoglycemic agent in diabetic mice. The hypoglycemic effect of this compound may be mediated, at least in part, by inhibiting the GP and G6Pase activities.

关 键 词：type 2 diabetes GENIPOSIDE glycogen phosphorylase GLUCOSE-6-PHOSPHATASE hepatic glucose-regulating enzymes hypoglycemic agents 

分 类 号：R587.1[医药卫生—内分泌]