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


CONCLUSIONS
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.
Wu
Shao-Yu
SY
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Wang
Guang-Fa
GF
Liu
Zhong-Qiu
ZQ
Rao
Jin-Jun
JJ
Lü
Lin
L
Xu
Wei
W
Wu
Shu-Guang
SG
Zhang
Jia-Jie
JJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000235:genetics / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D039823:Iridoids / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011897:Random Allocation; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D039823:Iridoids; D014280:Triglycerides; C007835:geniposide; D002784:Cholesterol; D024981:Glycogen Phosphorylase; D005952:Glucose-6-Phosphatase