Effects of Sodium dependent Glucose Transporter 2 (SGLT2) Inhibition with Empagliflozin on Oxidative Stress and Endothelial Dysfunction in STZ-Induced Type I Diabetic Rat

2013 ◽  
Vol 65 ◽  
pp. S31-S32
Author(s):  
Matthias Oelze ◽  
Swenja Kröller-Schön ◽  
Yulyia Mikhed ◽  
Michael Mader ◽  
Elena Zinßius ◽  
...  
2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
M Oelze ◽  
S Kröller-Schön ◽  
M Mader ◽  
E Zinßius ◽  
P Stamm ◽  
...  

2011 ◽  
Vol 13 (4) ◽  
pp. 576-584 ◽  
Author(s):  
Tristan S. Maurer ◽  
Avijit Ghosh ◽  
Nahor Haddish-Berhane ◽  
Aarti Sawant-Basak ◽  
Carine M. Boustany-Kari ◽  
...  

Author(s):  
Hans-Joachim Anders ◽  
Anna Julie Peired ◽  
Paola Romagnani

Abstract In 2020, the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial first demonstrated that inhibition of the sodium–glucose transporter-2 (SGLT2) with dapagliflozin attenuates the progression of chronic kidney disease (CKD) with proteinuria in patients with or without diabetes at an unprecedented effect size. These results have far-reaching implications for a series of traditional concepts in Nephrology. It now became obvious that CKD with and without diabetes involves a predominant SGLT2-driven pathophysiology compared with the other pathogenic pathways currently under consideration. As SGLT2 inhibition is similarly efficacious in diabetic and non-diabetic CKD with proteinuria, treating CKD rather than ‘diabetic nephropathy’ becomes the central paradigm. Indeed, in older adults with type 2 diabetes, CKD is rather of multifactorial origin. As the DAPA-CKD trial included more patients with immunoglobulin A nephropathy (IgAN) than any of the previous IgAN trials, dual renin-angiotensin/SGLT2 inhibition may become the new standard. The same applies for patients with podocytopathy-related focal segmental glomerulosclerosis lesions. From now on, IgAN and podocytopathy trials without SGLT2 inhibition as background therapy and without glomerular filtration rate decline as primary outcome criterion will be of limited value. These and other potential implications will trigger broad discussions and secondary research activities with conclusions difficult to predict today. However, one is for sure: Nephrology after the DAPA-CKD trial will be not the same as it was before. Finally!


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Pardeep Kumar

Abstract Background and Aims The present study investigated the effects of silver nanoparticles on serum parameters of renal function, on oxidative stress markers (malondialdehyde [MDA] and 8-isoprostane), and on expression level of insulin receptor, glucose transporter 2 (GLUT2), glucokinase genes and heat-shock proteins (HSPs) in rats. Method Male Wistar rats (n=64, 10 weeks old) were divided into four groups. Group 1 received a standard diet (12% of calories as fat). Group 2 received a standard diet, plus silver nanoparticles (SNPs); received a single daily oral dose of SNP of 100 mg/kg in suspension. Group 3 received a high-fat diet (40% of calories as fat) for 2 weeks, and was then injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg intraperitoneally). Group 4 was treated in the same way as group 3 (HFD/STZ), but was supplemented with SNP 100mg /kg/body weight/day. Oxidative stress in the kidneys of diabetic rats was evidenced by an elevation in levels of MDA and 8-isoprostane. Protein concentrations of insulin receptor, GLUT2, glucokinase genes and heat-shock (HSP60 and HSP70) in renal tissue were determined by Western blot analyses. Results SNP supplementation lowered kidney concentrations of MDA, 8-isoprostane levels, serum urea-N, and creatinine, and reduced the severity of renal damage in the STZ-treated group (i.e., the diabetes-induced group). The expression of insulin receptor, GLUT-2, glucokinase genes and HSPs was lower in the STZ group that received SNP than in the group that did not. No significant effect of SNP supplementation was detected in regard to the overall measured parameters in the control group. Conclusion This study supported the efficacy of SNP in reducing renal risk factors and impairment because of diabetes and act as potent antidiabetic agent.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Philipp Welschof ◽  
Matthias Oelze ◽  
Swenja Kröller-Schön ◽  
Thomas Jansen ◽  
Michael Hausding ◽  
...  

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.


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