Abstract
BackgroundHyperglycaemia associated with myocardial oxidative stress and fibrosis is the main cause of diabetic cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor has recently been reported to improve glycaemic control in patients with type 2 diabetes in an insulin-independent manner. The aim of this study was to investigate the effect of empagliflozin on myocardium injury and the potential mechanism in type 2 diabetic KK-Ay mice.MethodsThirty diabetic KK-Ay mice were administered empagliflozin (10 mg/kg/day) by oral gavage daily for 8 weeks. After 8 weeks, heart structure and function were evaluated by echocardiography. Oxidants and antioxidants were measured and cardiac fibrosis was analysed using immunohistochemistry, Masson’s trichrome stain and Western blot.ResultsResults showed that empagliflozin improved diabetic myocardial structure and function, decreased myocardial oxidative stress and ameliorated myocardial fibrosis. Further study indicated that empagliflozin suppressed oxidative stress and fibrosis through inhibition of the transforming growth factor β/Smad pathway and activation of Nrf2/ARE signaling.ConclusionsGlycaemic control with empagliflozin significantly ameliorated myocardial oxidative stress injury and cardiac fibrosis in diabetic mice. Taken together, these results indicate that the empagliflozin is a promising agent for the prevention and treatment of diabetic cardiomyopathy.
Highlights
The global incidence of diabetes mellitus (DM) has gradually increased over the past three decades and has become a major public health problem worldwide [1]
Body weight was measured throughout the study, and body weight gain was calculated after 8 weeks of treatment
The body weight gain decreased in the mice of the DM + EM group and was significantly affected by empagliflozin therapy in the DM + EM group
Summary
The global incidence of diabetes mellitus (DM) has gradually increased over the past three decades and has become a major public health problem worldwide [1]. Oxidative stress is known to be associated with the development of diabetes. A growing body of evidence suggests an increase in oxidative stress in response to hyperglycaemia in vascular tissues of patients with DM [6, 7]. Several reports have shown that an increased level of reactive oxygen species (ROS), induced by hyperglycaemia, leads to impaired contractile function and myocardial fibrosis in the left ventricle of diabetic rats [8, 9]. The extent of myocardial fibrosis is associated with impairment in cardiac contractile function. To prevent the development of diabetic cardiomyopathy, more effective therapies should be used both to manage blood glucose to near-normal levels and reduce oxidative stress. Hyperglycaemia associated with myocardial oxidative stress and fibrosis is the main cause of diabetic cardiomyopathy. The aim of this study was to investigate the effect of empagliflozin on myocardium injury and the potential mechanism in type 2 diabetic KK-Ay mice
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