Endocrine Abstracts

We have reported that the anti-hyperglycaemic effects of Syzygium cordatum leaf triterpene mixtures (oleanolic acid (OA) and ursolic acid) in streptozotocin (STZ)-induced diabetic rats are mediated in part via increased hepatic glycogen synthesis. To further elucidate the mechanism(s) of the hypoglycaemic effects of the triterpene, this study investigated the effects of plant derived OA on glycogenic enzyme activities in STZ-induced diabetic rats. Pure OA was obtained from Syzygium aromaticum flower bud ethyl acetate solubles following recrystallization with ethanol and its structure confirmed by spectroscopic analysis using 1D and 2D, ¹H and ¹³C Nuclear Magnetic Resonance (NMR) techniques. Hepatic and gastrocnemius muscle glycogen concentrations and activities of hexokinase and glucokinase enzymes were measured in separate groups of non-diabetic and STZ-induced diabetic rats after 5 weeks of twice-daily treatment with OA (60 mg/kg. p.o). Rats treated with deionised water (3 ml/kg p.o.), or standard hypoglycaemic drugs (insulin, 200 μg/kg, s.c.; metformin, 500 mg/kg, p.o.) acted as untreated and treated positive controls, respectively. Hexokinase and glucokinase activities were measured spectrophotometrically in reactions where the oxidation of glucose-6-phosphate formed was coupled to NADP⁺ reduction catalyzed by glucose-6-phosphate dehydrogenase. OA increased hepatic and muscle glycogen concentrations of both non-diabetic and STZ-induced diabetic rats (P<0.05) as did standard drugs, metformin and insulin. OA and insulin significantly increased muscle hexokinase activity in the non diabetic animals. There was no significant effect on muscle hexokinase activity with all treatments in the STZ-induced diabetic animals, however; metformin showed a significant decrease in hexokinase activity compared to control animals (P<0.05). On the contrary, OA and insulin significantly increased hepatic hexokinase and glucokinase activities in STZ-induced diabetic rats. These findings suggest that the plant-derived OA increases glycogen synthesis, partly by increasing the activities of the enzymes hexokinase and glucokinase in the muscle and liver, respectively thereby reducing blood glucose levels.