Zeynep Elif YESILYURT-DIRICAN, Irem KARAOMERLIOGLU, Betül Rabia ERDOGAN-VADACCA, Gaye OZTURK, Martin Christian MICHEL, Ebru ARIOGLU-INAN
Journal of Research in Pharmacy - 2026;30(1):60-71
Diabetes mellitus leads to cardiovascular complications including impaired cardiac beta -adrenoceptor (beta -AR) function. Sodium -glucose cotransporter -2 (SGLT2) inhibitors, such as empagliflozin (EMPA), improve outcomes in heart failure patients and animal models. Therefore, we have investigated the effects of EMPA on in vivo cardiac function and beta-AR mediated contractile responses in streptozotocin (STZ) -induced diabetes in a design reflecting late -onset of treatment. Male Sprague Dawley rats were divided into 4 groups (control, EMPA -treated control, diabetic, and EMPA -treated diabetic). Diabetes was induced by STZ injection (40 mg/kg). 13 -16 weeks after STZ injection, a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. At the end of the treatment period, in vivo cardiac function was evaluated by pressure -volume (PV) loop analysis and beta -AR mediated contractile response was determined by isoprenaline on isolated papillary strips. The blood glucose -lowering effect of low-dose EMPA was confirmed. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contraction and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some (e.g., stroke volume, ejection fraction, cardiac index) but not all parameters. Our results indicate that low -dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes has manifested. Future studies using a preventive rather than therapeutic approach could help to clarify the possible benefits of EMPA on the diabetic heart.
