The Potential Cardio-Protective Effects of Canagliflozin alone and in combination with metformin on Fructose induced Insulin resistance in Rats.

[摘要] Diabetic cardiovascular complications are a leading cause for increased morbidity and mortality.Diabetic cardiomyopathy is one of these complications which develop independently of coronary arterydisease or hypertension. Previous studies stated the potential role of a state of inflammation via upregulationof NF-kB. The extra pancreatic, diuretic effect of canagliflozin, a SGLT2 inhibitor, appears promising intreatment of diabetic cardiomyopathy or reversing cardiovascular side effects of insulin sensitizers. This studywas designed to investigate the potential cardio-protective effects of canagliflozin alone and in combinationwith metformin on fructose induced rat model of insulin resistance. Forty male albino rats were divided into 5groups: normal control group, non-treated fructose induced diabetic group, canagliflozin treated group (28mg/kg/day), metformin treated group (250 mg/ kg /day) and canagliflozin+ metformin treated group. All drugswere given p.o. for 4 weeks. Insulin resistance parameters, lipid profile, BP, LV wall thickness, Lead II ECG,histopathological study of the cardiac tissue and GSH and NF-kB concentrations in LV tissue homogenate wereinvestigated. Canagliflozin+ metformin combination showed more significant improvement ofelectrophysiological and biochemical parameters which were confirmed with histopathological examinationthan other groups, suggesting a very promising role of this combination in treatment of insulin resistance.

[学科分类] 工程和技术（综合）

[关键词] Diabetes;Canagliflozin;Metformin;Cardiomyopathy;NF-kB.