Comparison of Sitagliptin with Vildagliptin's effects on Mitochondrial Activity, Heart Rate Variability, and Cardiac Performance in Obese Insulin-Resistant Rats

Abstract

Context and Objective: It has been demonstrated that a prolonged high-fat diet (HFD) can lead to insulin resistance, which is typified by hyperinsulinemia and metabolic inflexibility. Heart failure, cardiac mitochondrial dysfunction, and cardiac sympathovagal imbalance are all linked to insulin resistance. Oral anti-diabetic medications called sitagliptin and vildagliptin, which block dipeptidyl peptidase-4 (DPP-4), are frequently administered to individuals suffering from cardiovascular disease. Thus, using a mouse model of insulin resistance, we aimed to investigate the effects of sitagliptin and vildagliptin in this work. Method of Experimentation: Male For a period of 12 weeks, 180–200 g Wistar rats were fed either an HFD (59% energy from fat) or a regular diet (20% energy from fat). After that, these rats were split up into three subgroups and given either vehicle for an additional 21 days, sitagliptin (30 mg/kg/day-1), vildagliptin (3 mg/kg−1 day−1), or both days. Heart rate variability (HRV), cardiac function, oxidative stress, metabolic parameters, and cardiac mitochondrial function were all measured Important Findings: In rats fed a high-fat diet (HFD), they developed insulin resistance, which was manifested as a decrease in high-density lipoprotein (HDL) and an increase in body weight, plasma insulin, total cholesterol, and oxidative stress levels. Furthermore, HFD rats showed evidence of cardiac dysfunction, decreased HRV, cardiac mitochondrial dysfunction, and alterations in cardiac mitochondrial morphology. Vildagliptin and sitagliptin both raised HDL levels while lowering plasma insulin, total cholesterol, and oxidative stress. Additionally, sitagliptin and vildagliptin fully restored HRV and reduced cardiac dysfunction as well as cardiac mitochondrial dysfunction Conclusions and Significance: In obese insulin-resistant rats, vildagliptin and sitagliptin both had comparable cardioprotective effects.