RGD Reference Report - Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat. - Rat Genome Database

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Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat.

Authors: Masuda, Takahiro  Watanabe, Yuko  Fukuda, Keiko  Watanabe, Minami  Onishi, Akira  Ohara, Ken  Imai, Toshimi  Koepsell, Hermann  Muto, Shigeaki  Vallon, Volker  Nagata, Daisuke 
Citation: Masuda T, etal., Am J Physiol Renal Physiol. 2018 May 23. doi: 10.1152/ajprenal.00143.2018.
RGD ID: 13673897
Pubmed: PMID:29790389   (View Abstract at PubMed)
PMCID: PMC6734084   (View Article at PubMed Central)
DOI: DOI:10.1152/ajprenal.00143.2018   (Journal Full-text)

The chronic intrinsic diuretic and natriuretic tone of sodium-glucose cotransporter 2 (SGLT2) inhibitors is incompletely understood, because their effect on body fluid volume (BFV) has not been fully evaluated and because they often increase food and fluid intake at the same time. Here we first compared the effect of the SGLT2 inhibitor ipragliflozin (Ipra, 0.01% in diet for 8 weeks) and vehicle (Veh) in Spontaneously Diabetic Torii rat, a non-obese type 2 diabetic model, and non-diabetic Sprague-Dawley rats. In non-diabetic rats, Ipra increased urinary excretion of Na+ (UNaV) and fluid (UV) associated with increased food and fluid intake. Diabetes increased these 4 parameters, but Ipra had no further effect; probably due to its antihyperglycemic effect, such that glucosuria and as a consequence food and fluid intake were unchanged. Fluid balance and BFV, determined by bioimpedance spectroscopy, were similar among the 4 groups. To study the impact of food and fluid intake, non-diabetic rats were treated for 7 days with Veh, Ipra or Ipra+pair-feeding+pair-drinking (Pair-Ipra). Pair-Ipra maintained a small increase in UV and UNaV versus Veh despite similar food and fluid intake. Pair-Ipra induced a negative fluid balance and decreased BFV, while Ipra or Veh had no significant effect compared with basal values. In conclusion, SGLT2 inhibition induces a sustained diuretic and natriuretic tone. Homeostatic mechanisms are activated to stabilize body fluid volume, including compensatory increases in fluid and food intake.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of urine volume  IMP 13673897 RGD 
renal potassium excretion  IMP 13673897 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc5a2  (solute carrier family 5 member 2)


Additional Information