Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin.
OBJECTIVE
Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) are important in control of blood glucose homeostasis, and are considered to be 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 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 GP and G6Pase activities.
Lv
Lin
L
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, PR China.
Wu
Shao-Yu
SY
Wang
Guang-Fa
GF
Zhang
Jia-Jie
JJ
Pang
Jian-Xin
JX
Liu
Zhong-Qiu
ZQ
Xu
Wei
W
Wu
Shu-Guang
SG
Rao
Jin-Jun
JJ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D012503:Saponins / Q000494:pharmacology*; D013311:Streptozocin; D014280:Triglycerides / Q000097:blood; D014315:Triterpenes / Q000494:pharmacology*
D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D007328:Insulin; D012503:Saponins; D014280:Triglycerides; D014315:Triterpenes; C052064:astragaloside A; D013311:Streptozocin; D002784:Cholesterol; D024981:Glycogen Phosphorylase; D005952:Glucose-6-Phosphatase