digilib@itb.ac.id +62 812 2508 8800

Recent studies indicated the involvement of arachidonic acid cascade in regulation of blood glucose. This study was aimed to confirm the involvement of arachidonic acid cascade in the pathophysiology of diabetes mellitus by assessing the effect of diclofenac, one of the cyclooxygenase (COX) enzym inhibitors. In dose orientation experiment, mice were divided into several groups, each was administrated vehicle, diclofenac, or glibenclamide. Blood glucose level was observed until 240 minutes after drug administration. Optimum dose and administration time obtained from this experiment was used in the subsequent tests, which consisted of glucose tolerance test, alloxan diabetes test, glucose tolerance test in alloxan-treated mice, and antagonistic activity against hyperglicemic factor. Diclofenac at l0 mg/kg bw suppressed blood glucose elevation in the first 30 minutes after its administration. Despite no improvement observed in glucose tolerance test under normal condition, diclofenac suppressed glucose level increase in glucose tolerance in alloxan-treated mice. Furthermore, diclofenac blocked exacerbation of hyperglycemia in alloxan-treated mice. However, diclofenac did not inhibit epinephrine- induced blood glucose elevation. Diclofenac at l0 mg/kg bw tended to show antihyperglicemic rather than hypoglicemic effect. This result indicated the involvement of arachidonic acid cascade in the pathophysiology of diabetes mellitus.