Dapagliflozin treatment in Type 1 diabetic rats reduced left cardiac chamber dilation, ventricular hypertrophy, and systolic/diastolic dysfunction but did not change sirtuin 3/6 expression.
Does dapagliflozin improve cardiac remodeling and modulate sirtuin expression in a rat model of type 1 diabetes mellitus?
Dapagliflozin attenuates adverse cardiac remodeling and dysfunction in a Type 1 diabetes rat model, independent of sirtuin 3 and 6 expression.
Abstract Introduction Inhibition of sodium-glucose co-transporter 2 (SGLT2) has cardiovascular benefits in patients with Type 2 diabetes mellitus (DM). The mechanisms involved in beneficial effects have not yet been fully clarified. Studies suggest that SGLT2 inhibitors interact with sirtuins, proteins that modulate cellular survival and apoptosis, autophagy, mitochondrial function, and stress response. In DM, sirtuin 3 improves mitochondrial function, oxidative stress, and insulin resistance. Few investigators have evaluated the cardiovascular effects of SGLT2 inhibition in Type 1 DM. Objective To analyze the effects of the SGLT2 inhibitor dapagliflozin (Dapa) on cardiac structure, ventricular function, and myocardial expression of sirtuins 3 and 6 in Type 1 DM rats. . Methods Male Wistar rats were divided into control (C), C treated with Dapa (C-Dapa), DM, and DM treated with Dapa (DM-Dapa) groups. DM was induced by a single streptozotocin injection, 50 mg/kg. Dapa was added to the diet at a dosage of 10 mg/kg/day for 16 weeks. Cardiac remodeling was evaluated by echocardiogram at the end of the study and protein expression by Western blot. Statistical analysis: ANOVA complemented by the Tukey or Kruskal–Wallis and Dunn tests (p0.05). Results Echocardiogram data are presented in the Table. Protein expression of sirtuins 3 and 6 did not differ between the groups. Conclusion Treatment with dapagliflozin attenuates left cardiac chambers dilation, left ventricular hypertrophy, and systolic and diastolic dysfunction, and does not modulate protein expression of myocardial sirtuins 3 and 6 in rats with Type 1 diabetes mellitus.
Marreiros et al. (2025) studied this question. Dapagliflozin treatment in Type 1 diabetic rats reduced left cardiac chamber dilation, ventricular hypertrophy, and systolic/diastolic dysfunction but did not change sirtuin 3/6 expression.