Effect of Dapagliflozin Treatment on the Expression of Renal Sodium Transporters/Channels on High-Fat Diet Diabetic Mice
| Autor: | Jeroen H. F. de Baaij, Bastiaan E. de Galan, Victor A. Gault, Chao Ma, Joost G. J. Hoenderop, René J. M. Bindels, Paul Millar |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Antiporter 030232 urology & nephrology Nephron 030204 cardiovascular system & hematology Diet High-Fat Streptozocin Diabetes Mellitus Experimental 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Glucosides Experimental Nephrology and Genetics: Original Paper Internal medicine Diabetes mellitus medicine Animals Distal convoluted tubule Dapagliflozin Benzhydryl Compounds Sodium-Glucose Transporter 2 Inhibitors business.industry Body Weight Sodium Membrane Transport Proteins Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] medicine.disease Streptozotocin medicine.anatomical_structure Endocrinology Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] chemistry Ascending limb of loop of Henle Sodium-Potassium-Exchanging ATPase business Cotransporter medicine.drug |
| Zdroj: | Nephron, 142, 51-60 Nephron, 142, 1, pp. 51-60 |
| ISSN: | 1660-8151 |
| Popis: | Background: Inhibition of the Na+/glucose co-transporter 2 is a new therapeutic strategy for diabetes. It is unclear how proximal loss of Na+ (and glucose) affects the subsequent Na+ transporters in the proximal tubule (PT), thick ascending limb of loop of Henle (TAL), distal convoluted tubule (DCT) and collecting duct (CD). Methods: Mice on a high fat diet were administered 3 doses streptozotocin 6 days prior to oral dapagliflozin administration or vehicle for 18 days. A control group of lean mice were also included. Body weight and glucose were recorded at regular intervals during treatment. Renal Na+ transporters expression in nephron segments were analyzed by RT-qPCR and Western blot. Results: Dapagliflozin treatment resulted in a significant reduction in body weight and blood glucose compared to vehicle-treated controls. mRNA results showed that Na+-hydrogen antiporter 3 (NHE3), Na+/phosphate cotransporter (NaPi-2a) and epithelial Na+ channel expression was increased, Ncx1, ENaCβ and ENaCγ expression declined (p all < 0.05), respectively, in dapagliflozin-treated mice when compared with saline vehicle mice. Na-K-2Cl cotransporters and Na-Cl cotransporter mRNA expression was not affected by dapagliflozin treatment. Na+/K+-ATPase (Atp1b1) expression was also increased significantly by dapagliflozin treatment, but it did not affect Atp1a1 and glucose transporter 2 expression. Western blot analysis showed that NaPi-2a, NHE3 and ATP1b1 expression was upregulated in dapagliflozin-treated diabetic mice when compared with saline vehicle mice (p < 0.05). Conclusion: Our findings suggest that dapagliflozin treatment augments compensatory changes in the renal PT in diabetic mice. |
| Databáze: | OpenAIRE |
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