scholarly journals Effect of Empagliflozin, a Selective Sodium-Glucose Cotransporter 2 Inhibitor, on Kidney and Peripheral Nerves in Streptozotocin-Induced Diabetic Rats

2018 ◽  
Vol 42 (4) ◽  
pp. 338 ◽  
Author(s):  
Kyung Ae Lee ◽  
Heung Yong Jin ◽  
Na Young Lee ◽  
Yu Ji Kim ◽  
Tae Sun Park
2021 ◽  
Vol 22 (15) ◽  
pp. 7774
Author(s):  
Sevil Korkmaz-Icöz ◽  
Cenk Kocer ◽  
Alex A. Sayour ◽  
Patricia Kraft ◽  
Mona I. Benker ◽  
...  

Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding canagliflozin (CANA) (an SGLT-2-inhibitor) to saline protects vascular grafts from IRI. Aortic rings from non-diabetic rats were isolated and immediately mounted in organ bath chambers (control, n = 9–10 rats) or underwent cold ischemic preservation in saline, supplemented either with a DMSO vehicle (IR, n = 8–10 rats) or 50µM CANA (IR + CANA, n = 9–11 rats). Vascular function was measured, the expression of 88 genes using PCR-array was analyzed, and feature selection using machine learning was applied. Impaired maximal vasorelaxation to acetylcholine in the IR-group compared to controls was significantly ameliorated by CANA (IR 31.7 ± 3.2% vs. IR + CANA 51.9 ± 2.5%, p < 0.05). IR altered the expression of 17 genes. Ccl2, Ccl3, Ccl4, CxCr4, Fos, Icam1, Il10, Il1a and Il1b have been found to have the highest interaction. Compared to controls, IR significantly upregulated the mRNA expressions of Il1a and Il6, which were reduced by 1.5- and 1.75-fold with CANA, respectively. CANA significantly prevented the upregulation of Cd40, downregulated NoxO1 gene expression, decreased ICAM-1 and nitrotyrosine, and increased PECAM-1 immunoreactivity. CANA alleviates endothelial dysfunction following IRI.


2017 ◽  
Vol 40 (7) ◽  
pp. 646-651 ◽  
Author(s):  
Tomoko Yoshikawa ◽  
Takuya Kishi ◽  
Keisuke Shinohara ◽  
Ko Takesue ◽  
Risa Shibata ◽  
...  

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S F Ewida ◽  
A M H Shabaan ◽  
H F Eldomiaty ◽  
G S Y Hanna ◽  
S E Hassabelnabi ◽  
...  

Abstract Background Cardiovascular disease is the most life-threatening diabetic complication. Type II diabetes may lead to damage of the heart muscle. Sodium glucose cotransporter 2 (SGL2) inhibitors are a new class of diabetic medications indicated only for the treatment of type II diabetes. Aim This investigation was assigned to compare the effect of metformin and SGL2 inhibitors (dapaglifilizone) in type II diabetic rats. Design and methods: Eighty rats divided into four groups were used: non diabetic; diabetic; diabetic metformin -treated; diabetic dapagliflizoline- treated. At the end, arterial blood pressure and cardiac performance (cardiac contractility and heart rate) were assessed. Serum glucose, glycosylated hemoglobin (HbA1c), insulin, lipid profile, total antioxidant capacity, malondialdehyde, tumor necrosis factor α were measured. HOMA-IR index was calculated. DNA changes were assessed from hearts and aortea. Aortic endothelial changes recorded using H&E and masson trichome techniques. Results Glycemic index, lipid profile, oxidative stress and inflammatory parameters were significantly improved in both metformin and dapagliflizoline treated groups with also significant improvement in blood pressure, Cardiac performance and reduction in collagen deposition in aortic tissue and DNA fragmentation. Dapagliflizoline treatment results were significantly improved in all parameters compared to metformin treatment. Conclusion SGL2 inhibitors (dapaglifilizone) successfully restored glycemic state, cardiac performance, DNA and endothelial changes in type II diabetic rats compared to metformin.


2008 ◽  
Vol 54 (4) ◽  
pp. 321-328 ◽  
Author(s):  
Xiao-pei CUI ◽  
Bao-ying LI ◽  
Hai-qing GAO ◽  
Na WEI ◽  
Wei-ling WANG ◽  
...  

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A439-A439
Author(s):  
Yoshiyu Takeda ◽  
Yoshimichi Takeda ◽  
Masashi Demura ◽  
Mitsuhiro Kometani ◽  
Shigehiro Karashima ◽  
...  

Abstract Objective: The renoprotective effect of sodium glucose cotransporter 2 inhibitor (SGL2i) has been reported in diabetic patients. Local renin-angiotensin-aldosterone system (RAAS) is activated in diabetes mellitus and hypertension. We examined the effects of SGL2i on the RAAS in the obese diabetic rats fed a high salt diet. Methods: Zucker-diabetic rats (ZDR) and control rats were fed a high or normal salt diet and were treated with canagliflozin for 8 weeks. Blood pressure (BP), blood glucose (BG), PRA, plasma aldosterone (PAC), urinary albumin excretion (UAE), urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), gene expression of angiotensinogen in the kidney were measured. Results: ZDR febd a high salt diet showed high BP, increased UAE and urinary 8-OHdG and elevated angiotensinogen mRNA levels. Treatment with canagliflozin significantly decreased BP, BG, UAE, urinary 8-OHdG and and renal angiotensinogen mRNA levels compared with control rats (p&lt0.05). Discussion and Conclusion: The closer mechanism of renoptotection of SGL2i in diabetes mellitus is unclear. We have reported that the repoprotective effects of type 2 angiotensin receptor antagonist or mineralocorticoid receptor blocker were partly due to the decreased RAAS in the kidney. Decreased renal RAAS by the treatment with canagliflozin may contribute to the renoprotection in DZR.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Horacio Osorio ◽  
Israel Coronel ◽  
Abraham Arellano ◽  
Ursino Pacheco ◽  
Rocío Bautista ◽  
...  

The hyperglycemia triggers several chronic diabetic complications mediated by increased oxidative stress that eventually causes diabetic nephropathy. The aim of this study was to examine if the sodium-glucose cotransporter (SGLT2) inhibition prevents the oxidative stress in the kidney of diabetic rats.Methods. The diabetic rat model was established by intraperitoneal injection of streptozotocin (50 mg/kg). The inhibition of SGLT2 was induced by daily subcutaneous administration of phlorizin (0.4 g/kg). Oxidative stress was assessed by catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities and by immunohistochemical analysis of 3-nitrotyrosine (3-NT).Results. Streptozotocin-induced diabetes caused hyperglycemia and lower body weight. The CAT activity decreased in cortex and medulla from diabetic rats; in contrast, the GPx activity increased. Furthermore the 3-NT staining of kidney from diabetic rats increased compared to control rats. The inhibition of SGLT2 decreased hyperglycemia. However, significant diuresis and glucosuria remain in diabetic rats. The phlorizin treatment restores the CAT and GPX activities and decreases 3-NT staining.Conclusion. The inhibition of SGLT2 by phlorizin prevents the hyperglycemia and oxidative stress in kidney of diabetic rats, suggesting a prooxidative mechanism related to SGLT2 activity.


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