Effect of Dapagliflozin Treatment on the Expression of Renal Sodium Transporters/Channels on High-Fat Diet Diabetic Mice

Overview

Journal Nephron

Publisher Karger

Specialty Nephrology

Date 2019 Feb 26

PMID 30799406

Citations 9

Authors

Chao Ma

Jeroen H F de Baaij

Paul J Millar

Victor A Gault

Bastiaan E de Galan

Rene J M Bindels

Joost G J Hoenderop

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis.

Koh E, Kim G, Chung S Endocrinol Metab (Seoul). 2023; 38(4):359-372.

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Empagliflozin increases kidney weight due to increased cell size in the proximal tubule S3 segment and the collecting duct.

Sinha F, Federlein A, Biesold A, Schwarzfischer M, Krieger K, Schweda F Front Pharmacol. 2023; 14:1118358.

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Gholam M, Liu L, Searcy L, Denslow N, Alli A Int J Mol Sci. 2023; 24(2).

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SGLT2 inhibition effect on salt-induced hypertension, RAAS, and Na transport in Dahl SS rats.

Kravtsova O, Bohovyk R, Levchenko V, Palygin O, Klemens C, Rieg T Am J Physiol Renal Physiol. 2022; 322(6):F692-F707.

PMID: 35466690 PMC: 9142161. DOI: 10.1152/ajprenal.00053.2022.

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