Abstract 412: The Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin Improves Diabetic Complications in the Streptozotocin Type 1 Diabetes Mellitus Model by Interfering With Glucotoxicity and Rescue of Beta-Cell Function
Objectives: In diabetes, cardiovascular complications are associated with endothelial dysfunction and oxidative stress. Empagliflozin (Empa), as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i) in clinical development, offers a promising novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with Empa could improve endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated oxidative stress.
Research Design and Methods: Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection Empa was administered via drinking water for 7 weeks.
Results: Treatment with Empa (10 and 30 mg/kg/d), showed reduction of blood glucose and a normalization of endothelial dysfunction (aortic rings) in diabetic rats and a reduced oxidative stress in aortic vessels (dihydroethidine staining) and in blood (phorbol ester/zymosan A-stimulated chemiluminescence). Additionally, the pro-inflammatory phenotype and glucotoxicity in diabetic animals was normalized by SGLT2i therapy.
Conclusion: In this study we could demonstrate that Empa improves hyperglycemia and prevents the development of endothelial dysfunction and oxidative stress in type 1 diabetic rats. Future studies will investigate the underlying mechanisms of these antioxidant and anti-inflammatory effects with special emphasis on low-grade inflammation, glucotoxicity and oxidative stress, all of which contributes to cardiovascular complications.
Author Disclosures: P. Welschof: None. M. Oelze: Other Research Support; Modest; Travel support as a speaker for Boehringer Ingelheim. S. Kröller-Schön: None. T. Jansen: None. M. Hausding: None. Y. Mikhed: None. P. Stamm: None. M. Mader: None. E. Zinßius: None. S. Agdauletova: None. P. Wenzel: None. E. Schulz: None. S. Bottari: None. E. Mayoux: Employment; Significant; employee of Boehringer Ingelheim. T. Münzel: Research Grant; Significant; research grant by Boehringer Ingelheim for preclinical study. A. Daiber: Research Grant; Significant; research grant by Boehringer Ingelheim for preclinical study.
- © 2014 by American Heart Association, Inc.