%0 Journal Article %1 masuda2018unmasking %A Masuda, T. %A Watanabe, Y. %A Fukuda, K. %A Watanabe, M. %A Onishi, A. %A Ohara, K. %A Imai, T. %A Koepsell, H. %A Muto, S. %A Vallon, V. %A Nagata, D. %D 2018 %J Am J Physiol Renal Physiol %K Animals myOwn %N 3 %P F653-F664 %R 10.1152/ajprenal.00143.2018 %T Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat %U https://www.ncbi.nlm.nih.gov/pubmed/29790389 %V 315 %X 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 wk) and vehicle (Veh) in Spontaneously Diabetic Torii rat, a nonobese type 2 diabetic model, and nondiabetic Sprague-Dawley rats. In nondiabetic rats, Ipra increased urinary excretion of Na(+) (UNaV) and fluid (UV) associated with increased food and fluid intake. Diabetes increased these four parameters, but Ipra had no further effect, probably because of 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 four groups. To study the impact of food and fluid intake, nondiabetic 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, whereas 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 BFV, including compensatory increases in fluid and food intake.

@article{masuda2018unmasking, abstract = {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 wk) and vehicle (Veh) in Spontaneously Diabetic Torii rat, a nonobese type 2 diabetic model, and nondiabetic Sprague-Dawley rats. In nondiabetic rats, Ipra increased urinary excretion of Na(+) (UNaV) and fluid (UV) associated with increased food and fluid intake. Diabetes increased these four parameters, but Ipra had no further effect, probably because of 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 four groups. To study the impact of food and fluid intake, nondiabetic 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, whereas 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 BFV, including compensatory increases in fluid and food intake.}, added-at = {2024-02-15T15:08:22.000+0100}, author = {Masuda, T. and Watanabe, Y. and Fukuda, K. and Watanabe, M. and Onishi, A. and Ohara, K. and Imai, T. and Koepsell, H. and Muto, S. and Vallon, V. and Nagata, D.}, biburl = {https://www.bibsonomy.org/bibtex/2ef76495e5c38f05d49b127ee2fcb3883/jvsi_all}, doi = {10.1152/ajprenal.00143.2018}, interhash = {5b3f3639b34248df4a94d5d7a12e8899}, intrahash = {ef76495e5c38f05d49b127ee2fcb3883}, issn = {1522-1466 (Electronic) 1931-857X (Print) 1522-1466 (Linking)}, journal = {Am J Physiol Renal Physiol}, keywords = {Animals myOwn}, note = {Masuda, Takahiro Watanabe, Yuko Fukuda, Keiko Watanabe, Minami Onishi, Akira Ohara, Ken Imai, Toshimi Koepsell, Hermann Muto, Shigeaki Vallon, Volker Nagata, Daisuke eng P30 DK079337/DK/NIDDK NIH HHS/ R01 DK106102/DK/NIDDK NIH HHS/ R01 DK112042/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2018/05/24 Am J Physiol Renal Physiol. 2018 Sep 1;315(3):F653-F664. doi: 10.1152/ajprenal.00143.2018. Epub 2018 May 23.}, number = 3, pages = {F653-F664}, timestamp = {2024-02-15T15:08:22.000+0100}, title = {Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat}, type = {Journal Article}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29790389}, volume = 315, year = 2018 }