Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Background Dapagliflozin is a sodium{u2013}glucose cotransporter 2 (SGLT2) inhibitor that is used for treating type 2 diabetes mellitus (T2DM), whereas lansoprazole, a proton pump inhibitor (PPI), is used as a traditional anti-ulcer drug.The use of PPIs is common among patients with T2DM to counter the increased risk of developing gastroesophageal reflux disease (GERD).Aim The present study investigated the possible antidiabetic effects of LPZ on fortified diet-fed/streptozotocin (FDF/STZ)-induced insulin resistant diabetic rats. Moreover, the study elucidated the underlying mechanism of action of LPZ and the beneficial role of its combination with the standard drug dapagliflozin (DAPA). Methods Insulin resistance was induced by feeding male adult Wistar rats with FDF for 1.5 months, followed by a single injection of low dose of STZ (35{u202F}mg/kg, i.p.). Insulin-resistant diabetic rats were orally treated with DAPA (1{u202F}mg/kg), LPZ (80{u202F}mg/kg), or DAPA (0.5 mg/kg) + LPZ (40 mg/kg) daily for 4 consecutive weeks. Results The combined administration of DAPA and LPZ normalized serum glucose, lipid profile, malondialdehyde (MDA) and leptin (LEP)levelsas well asmodified homeostasis model assessment of insulin resistance using C-peptide (HOMA (CP)-IR) and pancreatic glucose transporter-2 (Glut-2) gene expression

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