Mechanisms of antihyperglycemic effect of p-methoxycinnamic acid in normal and streptozotocin-induced diabetic rats.
We investigated the antihyperglycemic effect of p-methoxycinnamic acid (p-MCA), a cinnamic acid derivative, on plasma glucose and insulin concentrations, activities of hepatic glucose-regulating enzymes and hepatic glycogen content in normal and streptozotocin (STZ)-induced diabetic rats. p-MCA (10-100 mg/kg, PO) dose-dependently decreased plasma glucose concentration in both normal and diabetic rats in the oral glucose tolerance test. To investigate the chronic effects of p-MCA on glucose metabolism, p-MCA (40 mg/kg, PO) was administered to normal and diabetic rats once a day for 4 weeks. p-MCA reduced plasma glucose concentration in diabetic rats, which was observed during the 4-week study. However, p-MCA treatment did not change plasma glucose concentrations in normal rats during the 4-week study. p-MCA also reduced the excessive activities of hepatic glucose-6-phosphatase, hepatic hexokinase, glucokinase and phosphofructokinase in diabetic rats and increased hepatic glycogen in these rats. In p-MCA-treated normal rats, there were no changes in the activities of hepatic glucose-regulating enzymes, hepatic glycogen and glucose-6-phosphate. Our findings suggested that p-MCA exert its antihyperglycemic effect by increasing insulin secretion and glycolysis, and by decreasing gluconeogenesis.
Adisakwattana
Sirichai
S
Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University. Henridunant-Rd. Pathumwan, Bangkok 10330, Thailand.
Roengsamran
Sophon
S
Hsu
Walter H
WH
Yibchok-anun
Sirintorn
S
D000818:Animals; D001786:Blood Glucose; D002934:Cinnamates / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats
D001786:Blood Glucose; D002934:Cinnamates; D007004:Hypoglycemic Agents; D008112:Liver Glycogen; C063318:4-methoxycinnamic acid; D017853:Phosphotransferases (Alcohol Group Acceptor); D005952:Glucose-6-Phosphatase