الفهرس 
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Abstract
Cardiovascular complications represent the main cause of hospitalization and death in diabetic patients. Diabetes causes both microvascular and macrovascular complications and diabetic cardiomyopathy. Previous studies have demonstrated that hyperglycemia, hyperlipidemia, chronic low-grade inflammation, and oxidative stress are involved in the pathogenesis of those complications. Canagliflozin, as a prototype SGLT2 inhibitors, has a unique mechanism of action in promoting renal glucose elimination. The extrapancreatic, diuretic effect of the drug appears promising in treatment of diabetic cardiomyopathy or reversing cardiovascular side effects of insulin sensitizers. The main aim of this work is to investigate the efficacy of canagliflozin on FBG, lipid profile in fructose induced rat model of insulin resistance. The tested drug was compared with prototypes of the main oral antidiabetic agents namely vildagliptin and pioglitazone. This may help to find the exact role of this new drug on the recommended ideal protocol of treatment type 2 diabetes. Therefore, different combinations of canagliflozin with either vildagliptin or pioglitazone were tested in order to determine the validity of such combinations on glycemic control, development of diabetic cardiomyopathy as well as reversing weight gain and cardiac hypertrophy induced by insulin sensitizers. This may help to point out suggestions as regards to the use of combined oral hypoglycemic agents in treatment of type 2 diabetes if single one failed. Forty two adult male albino rats were divided into 7 groups. All animals except group 1 received high fructose diet (60%) for 8 weeks as a method for induction of type 2 diabetes. The first two groups were normal control group and non treated fructose induced diabetic group. The following 3 groups received monotherapy with canagliflozin, vildagliptin or pioglitazone. The last two groups received dual therapy with canagliflozin / vildagliptin and canagliflozin / pioglitazone respectively. To fulfill above mentioned aims, we investigated insulin resistance parameters (FBG, total body weight, HOMA-IR index and HbA1c), Lipid profile (total, LDL and HDL cholesterol and triglycerides), systolic, diastolic, mean arterial blood pressure, height of R wave on lead II of ECG, left ventricular wall thickness, cardiac tissue homogenate concentration of GSH and NF-kB and histopathological study of cardiac muscle.