الفهرس 
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Abstract
Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor; it reduces the glucose reabsorption from the kidney, and increases the glucose excretion in urine. This inhibitor has a unique insulin-independent mechanism, and is potentially a new method for the treatment of hyperglycemia in diabetic patients. In the present study, we investigated the therapeutic effect of the SGLT2 selective inhibitor, dapagliflozin in combination with low insulin dose compared with full dose of insulin treatment alone and dapagliflozin alone in diabetes type 1 rat model. Type 1 diabetes was induced by a single intraperitoneal injection of 60 mg/kg streptozotocin (STZ). The STZ-induced diabetic rats showed marked hyperglycemia and other metabolic abnormalities. Also, hepatic cytochrome P450 (CYP) 2E and CYP1A activities were increased while there was no change in CYP3A activity. We clarified the hypoglycemic effect of the combined treatment of dapagliflozin with a low dose of insulin compared with dapagliflozin alone and insulin alone in a 3-week and 8-week studies. The obtained results showed that dapagliflozin in combination with a low dose of insulin significantly lowered hyperglycemia, hypercholesterolemia, and hypertriglyceridemia. Furthermore, the antioxidant status, body weight, CYP2E and CYP1A activities were improved similar to full dose insulin treatment. By contrast, treatment with dapagliflozin alone did not improve the blood glucose levels, lipid profile, antioxidant status, body weight or CYP activities. These findings suggest that the dapagliflozin plus low insulin dose combination treatment exerts beneficial effect on blood glucose, lipid profile, antioxidant status, body weight and CYP450 enzymes activities similar to full insulin dose treatment in type 1 diabetes. However, administering dapagliflozin alone do not achieve a significant effect.