Endocrine Abstracts

Diabetes mellitus is characterized by partial or total deficiency of insulin resulting in derangement of carbohydrate metabolism and a decrease in the activity of glycogenic enzymes resulting in depletion of liver and muscle glycogen. Accordingly, this study assessed the influence of OA on two key glycogenic enzymes of skeletal muscle and liver tissues in STZ-induced diabetic rats. We have, however, reported that the anti-hyperglycaemic effects of Syzygium aromaticum derived oleanolic acid (OA) in streptozotocin (STZ)-induced diabetic rats are mediated in part via increased hepatic glycogen synthesis. Hepatic and gastrocnemius muscle glycogen concentrations and activities of glucokinase (GK) and hexokinase (HK) of STZ-induced diabetic rats were measured after 5 weeks of twice daily treatment with OA (80 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. HK and GK 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. After 5 weeks STZ-induced diabetic rats exhibited depleted glycogen levels and low activities of glycogenic enzymes in muscle and hepatic tissues. OA administration increased the activity of glycogenic enzymes with concomitant restoration of muscle and hepatic glycogen concentrations to near normalcy. Interestingly, the combination of OA and insulin did not significantly alter the activities of HK and GK of STZ-induced diabetic rats suggesting that that glycogen synthesis can also occur from precursors such as amino acids or fructose and lactate. Our data suggest that OA administration restores the activity of key glycogenic enzymes in the liver and skeletal muscle of STZ-induced diabetic rats to enhance glycogen synthesis to improve the glycaemic status. The restoration of this principal glucose utilization pathway by OA will constitute a novel therapeutic strategy for diabetes treatment.