{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:18:02Z","timestamp":1773832682894,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Clinical studies have shown that treatment with inhibitors of sodium\u2013glucose cotransporter\u00a02 (SGLT2) significantly increases the hematocrit in patients with type\u00a02 diabetes. To investigate whether SGLT2 inhibitors directly promote erythropoietin production independently on blood glucose reduction, the hematopoietic effect of the specific SGLT2 inhibitor, luseogliflozin, was examined in non\u2010diabetic rats with renal anemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Renal anemia was induced by treatment with adenine (200 or 600\u00a0mg\/kg\/day, orally for 10\u00a0days) in non\u2010diabetic Wistar\u2013Kyoto or Wistar rats, respectively. Luseogliflozin (10\u00a0mg\/kg bodyweight) or vehicle (0.5% carboxymethyl cellulose) was then administered for 6\u00a0weeks. The hematocrit and the hemoglobin (Hb), blood urea nitrogen, plasma creatinine, and plasma erythropoietin levels were monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with adenine decreased the hematocrit and the Hb level, which were associated with increases in the blood urea nitrogen and plasma creatinine levels. In Wistar\u2013Kyoto rats treated with 200\u00a0mg\/kg\/day adenine, administration of luseogliflozin induced glycosuria, but did not change the blood urea nitrogen, plasma creatinine levels, hematocrit, Hb or plasma erythropoietin levels. Similarly, luseogliflozin treatment failed to change the hematocrit or the Hb levels in Wistar rats with renal anemia induced by 600\u00a0mg\/kg\/day of adenine. Plasma erythropoietin concentrations were also not different between luseogliflozin\u2010 and vehicle\u2010treated rats. Similarly, in human erythropoietin\u2010producing cells derived from pluripotent stem cells, luseogliflozin treatment did not change the erythropoietin level in the medium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that SGLT2 inhibitor fails to exert hematopoietic effects in non\u2010diabetic conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13205","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T16:19:41Z","timestamp":1577463581000},"page":"834-843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Failure to confirm a sodium\u2013glucose cotransporter\u00a02 inhibitor\u2010induced hematopoietic effect in non\u2010diabetic rats with renal anemia"],"prefix":"10.1111","volume":"11","author":[{"given":"Daisuke","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine 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