{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:45:41Z","timestamp":1792813541157,"version":"4.5.0"},"reference-count":20,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2014,1,15]]},"abstract":"<jats:p>\n                    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for &gt;90 and \u223c3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40\u201350%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1\u2212\/\u2212) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose\/creatinine ratios in Sglt1\u2212\/\u2212 vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1\u2212\/\u2212 vs. WT after 24 h (\u221233 vs. \u221211%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC\n                    <jats:sub>50<\/jats:sub>\n                    for SGLT2 in mice, which were associated with FGR of 64 \u00b1 2% in WT and 17 \u00b1 2% in Sglt1\u2212\/\u2212. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations \u223c10-fold and reduced FGR to 44 \u00b1 3% in WT and to \u22121 \u00b1 3% in Sglt1\u2212\/\u2212. The absence of renal glucose reabsorption was confirmed in male and female Sglt1\/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50\u201360% of filtered glucose is excreted.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00518.2013","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T00:51:59Z","timestamp":1384390319000},"page":"F188-F193","source":"Crossref","is-referenced-by-count":290,"title":["Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia"],"prefix":"10.1152","volume":"306","author":[{"given":"Timo","family":"Rieg","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California;"},{"name":"Veterans Affairs San Diego Healthcare System, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California;"},{"name":"Veterans Affairs San Diego Healthcare System, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gerasimova","sequence":"additional","affiliation":[{"name":"Veterans Affairs San Diego Healthcare System, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Mayoux","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Biberach an der Riss, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Platt","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals, Incorporated, The Woodlands, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Powell","sequence":"additional","affiliation":[{"name":"Lexicon Pharmaceuticals, Incorporated, The Woodlands, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California;"},{"name":"Veterans Affairs San Diego Healthcare System, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Koepsell","sequence":"additional","affiliation":[{"name":"Department of Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Vallon","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California;"},{"name":"Department of Pharmacology, University of California San Diego, La Jolla, California;"},{"name":"Veterans Affairs San Diego Healthcare System, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00180.2008"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01511.x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1029"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01517.x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12073"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212240200"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00388.2010"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.251"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0052"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010080888"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0473"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00439.2012"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00259.2012"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.04010609"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01406.x"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00520.2013"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010030246"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00409.2012"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e32833bec06"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2009"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00518.2013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T19:51:43Z","timestamp":1567972303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00518.2013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,15]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,1,15]]}},"alternative-id":["10.1152\/ajprenal.00518.2013"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00518.2013","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,15]]}}}