{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:12:18Z","timestamp":1780492338834,"version":"3.54.1"},"reference-count":21,"publisher":"American Physiological Society","issue":"2","funder":[{"name":"NIH","award":["R01DK112042"],"award-info":[{"award-number":["R01DK112042"]}]},{"name":"NIH","award":["R01DK106102"],"award-info":[{"award-number":["R01DK106102"]}]},{"name":"NIH","award":["P30DK079337"],"award-info":[{"award-number":["P30DK079337"]}]},{"name":"Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach"},{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"crossref","award":["IP-11-2013-1481 (AGEMETAR)"],"award-info":[{"award-number":["IP-11-2013-1481 (AGEMETAR)"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:p> The sodium-glucose cotransporter SGLT2 inhibitor empagliflozin (plasma protein binding ~88%) may reach its target in the brush border of the early proximal tubule by glomerular filtration and tubular secretion. Here we determined whether empagliflozin is secreted by renal tubules in mice and whether genetic knockout of the basolateral organic anion transporter 3 ( Oat3\u2212\/\u2212) affects its tubular secretion or glucosuric effect. Renal clearance studies in wild-type (WT) mice showed that tubular secretion accounted for 50\u201370% of empagliflozin urinary excretion. Immunostaining indicated that SGLT2 and OAT3 localization partially overlapped in proximal tubule S1 and S2 segments. Glucosuria in metabolic cage studies was reduced in Oat3\u2212\/\u2212 vs. WT mice for acute empagliflozin doses of 1, 3, and 10 mg\/kg, whereas 30 mg\/kg induced similar maximal glucosuria in both genotypes. Chronic application of empagliflozin (~25 mg\u00b7kg<jats:sup>\u22121<\/jats:sup> \u00b7day<jats:sup>\u22121<\/jats:sup>) in Oat3\u2212\/\u2212 mice was associated with lower urinary glucose-to-creatinine ratios despite maintaining slightly higher blood glucose levels than WT. On a whole kidney level, renal secretion of empagliflozin was largely unchanged in Oat3\u2212\/\u2212 mice. However, the absence of OAT3 attenuated the influence of empagliflozin on fractional glucose excretion; higher levels of plasma or filtered empagliflozin were needed to induce similar increases in fractional renal glucose excretion. We conclude that empagliflozin is excreted into the urine to similar extent by glomerular filtration and tubular secretion. The latter can occur largely independent of OAT3. However, OAT3 increases the glucosuric effect of empagliflozin, which may relate to the partial overlap of its localization with SGLT2 and thus OAT3-mediated tubular secretion of empagliflozin in the early proximal tubule. <\/jats:p>","DOI":"10.1152\/ajprenal.00503.2017","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T13:19:51Z","timestamp":1518009591000},"page":"F386-F394","source":"Crossref","is-referenced-by-count":37,"title":["Organic anion transporter OAT3 enhances the glucosuric effect of the SGLT2 inhibitor empagliflozin"],"prefix":"10.1152","volume":"315","author":[{"given":"Yiling","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davorka","family":"Breljak","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Onishi","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falk","family":"Batz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panai","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Mayoux","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma, Biberach an der Riss, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Koepsell","sequence":"additional","affiliation":[{"name":"Department of Molecular Plant Physiology and 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