Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus

Abstract

Clinical trials have shown that sodium glucose co-transporter 2 (SGLT2) inhibitors improve clinical outcomes in diabetes mellitus (DM) patients. As most studies were performed in Type 2 DM, the cardiovascular effects of SGLT2 inhibition still require clarification in Type 1 DM. We analyzed the effects of SGLT2 inhibitor dapagliflozin on cardiac remodeling in rats with streptozotocin-induced diabetes, an experimental model of Type 1 DM. Methods: Male Wistar rats were assigned into four groups: control (C, n = 14); control treated with dapagliflozin (C + DAPA, n = 14); diabetes (DM, n = 20); and diabetes treated with dapagliflozin (DM + DAPA, n = 20) for 8 weeks. Dapagliflozin dosage was 5 mg/kg/day. Statistical analyses: ANOVA and Tukey or Kruskal–Wallis and Dunn. Results: DM + DAPA presented decreased blood pressure and glycemia and increased body weight compared to DM (C 507 ± 52; C + DAPA 474 ± 50; DM 381 ± 52 *; DM + DAPA 430 ± 48 # g; * p p p p < 0.05 vs. DM) and higher superoxide dismutase and glutathione peroxidase activity than DM. Advanced glycation end products did not differ between groups. Conclusion: Dapagliflozin is safe, increases body weight, decreases glycemia and oxidative stress, and attenuates cardiac remodeling in an experimental rat model of Type 1 diabetes mellitus.

Keywords

• SGLT2 inhibitor
• ventricular remodeling
• oxidative stress
• myocardial fibrosis
• dapagliflozin
• cardiac function