Combined Therapy with Insulin and Vildagliptin causes Cardiac Dysfunction in Diabetic Rats

Abstract

There is a strong rationale for using incretin-based therapies with insulin. In particular, hypoglycaemia is the limiting factor in glycemic management of insulin-treated patients of type 2 diabetes mellitus. The present study aimed at gaining greater understanding of the progression of cardiovascular degeneration in diabetes mellitus under combined treatment with vildalgliptin and insulin through various analyses on cardiac tissues such as triphenyl tetrazolium chloride dye test. Experimental diabetic rats exhibited significantly lower TCA cycle enzyme and antioxidant defence enzyme activities with a concomitant increase in lipid peroxidation of the heart tissue. Monotherapy with either vildagliptin or insulin prevented these alteration in the oxidative energy metabolism and restored the TCA cycle enzyme activities to near normal in alloxan diabetic rats whereas the combined therapy altered mitochondrial enzyme levels significantly. These findings suggested that the toxic effects of the combinatorial therapy could be attributed to an increased oxidative damage and altered mitochondrial energy production, which might lead to progression of cardiovascular disease.