The aim of the present study was to determine the effect of resveratrol on dipeptidyl peptidase 4 (DPP-4) and phosphoenolpyruvate carboxykinase (PEPCK) enzyme activities in streptozotocin (STZ) induced diabetic rats, trying to find an explanation for its hypoglycemic effect. Sixty male Wistar Albino rats were included in the present study and classified into three groups, group I (control,non-diabetic), group II (diabetic group),group ІІІ (diabetic rats treated with resveratrol, 5 mg/kg body weight/day) for 30 days. After 30 days, blood was collected for determination of; serum glucose, insulin and DPP-4 enzyme activity. The liver was excised for estimation of liver glycogen and PEPCK enzyme activity. Serum glucose, DPP-4 activity, and liver PEPCK activity were significantly increased but serum insulin and liver glycogen were significantly decreased in STZ treated group, while upon resveratrol treatment , they were all reversed with no significant difference between group I and group III (except for final fasting serum glucose level). Conclusion the antihyperglycemic effect of resveratrol may be related to its stimulatory effect on insulin ,its suppressive effect on :either DPP-4, so increases the level of incretins with subsequent increase in insulin release followed by lowering blood glucose level ,or its inhibitory effect on PEPCK enzyme activity and subsequent decrease in gluconeogenesis, or, finally its stimulation of glucose utilization by increasing glycogen formation.
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