755MOLECULAR MECHANISMS OF FLUOXETINE ANTIDIABETOGENIC EFFECTS IN STREPTOZOTOCIN –INDUCED DIABETIC RATSFluoxetine (PROZAC ® ), a selective serotonin reuptake inhibitor antidepressant used for the treatment of mood and anxiety disorders. No definite mechanisms have been elucidated for the associated hypoglycemia. Thus, the present study investigated the molecular mechanisms that underline fluoxetine treatment in streptozotocin (STZ)-diabetic and non- diabetic rats. Forty male albino rats were divided into four groups (n=10): the first one was normal control, the second one received fluoxetine. Diabetes type II was induced using STZ in the remaining groups and the 4 th one was treated orally with fluoxetine for 21 days. Blood glucose was decreased in hyper -glycemic but not normo-glycemic animals. The gene expression of pancreatic insulin; hepatic insulin receptor A; glucose transporters: GLUT-2 and GLUT-4 were increased. Moreover, blood insulin and lipid profile were improved in fluoxetine-treated diabetic rats. Conclusion: fluoxetine has anti-diabetogeic effect determined from the enhancement of insulin synthesis, insulin release, insulin receptors sensitivity and glucose uptakedr.mmeldeib@yahoo.comResearch762016Fluoxetine,Diabetes,Insulin,Insulin receptor A,GLUT-2,GLUT-4,RT- PCRMaha M. El DeibCentral Lab, Department of Biochemistry, Faculty of Vet. Med., Zagazig University, Egypt