title: Effect of Dapagliflozin Treatment on Fluid and Electrolyte Balance in Diabetic Rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Department of Internal Medicine & Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: LaRocque
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Orhan
authors.initials: O
authors.lastname: Efe
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Department of Physiology, Emory University School of Medicine, Atlanta, Georgia. Electronic address: jeff.sands@emory.edu.
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Sands
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Department of Physiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006029:Glycosuria / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D064466:Solute Carrier Family 12, Member 1 / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects*; D000096982:Urea Transporters
chemical_list: D051399:Aquaporin 2; D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D026901:Membrane Transport Proteins; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D064466:Solute Carrier Family 12, Member 1; D000096982:Urea Transporters; C496025:Aqp2 protein, rat; C578716:Slc12a1 protein, rat; C529054:dapagliflozin
keywords: Diabetes mellitus; Kidney; Sodium glucose cotransporter 2; Urine concentration