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Author Notes:

Address for correspondence: Dr. Jeff M. Sands, Emory University School of Medicine, Renal Division, 1639 Pierce Drive, NE, WMB room 338, Atlanta, GA 30322 USA, Phone: 404-727-2525, FAX: 404-727-3425, jeff.sands@emory.edu

The authors have no financial or other conflicts of interest to disclose.

Subject:

Research Funding:

This work was supported by NIH grants DK41707 and DK89828

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, General & Internal
  • General & Internal Medicine
  • Diabetes mellitus
  • Kidney
  • Sodium glucose cotransporter 2
  • Urine concentration
  • CISPLATIN-INDUCED POLYURIA
  • SGLT2 INHIBITOR
  • URINE CONCENTRATION
  • GLUCOSE-TRANSPORT
  • UREA TRANSPORTER
  • TUBULAR CELLS
  • NITRIC-OXIDE
  • SODIUM
  • EXPRESSION
  • NEPHROPATHY

Effect of Dapagliflozin Treatment on Fluid and Electrolyte Balance in Diabetic Rats

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Journal Title:

The American Journal of the Medical Sciences

Volume:

Volume 352, Number 5

Publisher:

, Pages 517-523

Type of Work:

Article | Post-print: After Peer Review

Abstract:

AIM: This study evaluates the effect of dapagliflozin, a SGLT2 inhibitor, on fluid or electrolyte balance and its effect on urea transporter-A1 (UT-A1), aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) protein abundance in diabetic rats. METHODS: Diabetes mellitus (DM) was induced by injection of streptozotocin into the tail vein. Serum Na+, K+, Cl- concentration, urine Na+, K+, Cl- excretion, blood glucose, urine glucose excretion, urine volume, urine osmolality and urine urea excretion were analyzed after the administration of dapagliflozin. UT-A1, AQP2 and NKCC2 proteins were detected by western blot. RESULTS: Dapagliflozin treatment decreased blood glucose concentration by 38% at day 7 and by 47% at day 14 and increased the urinary glucose excretion rate compared with the untreated diabetic animals. Increased 24-hour urine volume, decreased urine osmolality and hyponatremia, hypokalemia and hypochloremia observed in diabetic rats were attenuated by dapagliflozin treatment. Western blot analysis showed that UT-A1, AQP2 and NKCC2 proteins are upregulated in DM rats over control rats; dapagliflozin treatment results in a further increase in inner medulla tip UT-A1 protein abundance by 42% at day 7 and by 46% at day 14, but it did not affect the DM-induced upregulation of AQP2 and NKCC2 proteins. CONCLUSION: Dapagliflozin treatment augmented the compensatory changes in medullary transport proteins in DM. These changes would tend to conserve solute and water even with persistent glycosuria. Therefore, diabetic rats treated with dapagliflozin have a mild osmotic diuresis compared to nondiabetic animals, but this does not result in an electrolyte disorder or significant volume depletion.

Copyright information:

© 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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