Failure to confirm a sodium-glucose cotransporter 2 inhibitor-induced hematopoietic effect in non-diabetic rats with renal anemia

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Title
Failure to confirm a sodium-glucose cotransporter 2 inhibitor-induced hematopoietic effect in non-diabetic rats with renal anemia
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Description

Abstract

Aims/introduction: Clinical studies have shown that treatment with inhibitors of sodium-glucose cotransporter 2 (SGLT2) significantly increases the hematocrit in patients with type 2 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-diabetic rats with renal anemia.

Materials and methods: Renal anemia was induced by treatment with adenine (200 or 600 mg/kg/day, orally for 10 days) in non-diabetic Wistar-Kyoto or Wistar rats, respectively. Luseogliflozin (10 mg/kg bodyweight) or vehicle (0.5% carboxymethyl cellulose) was then administered for 6 weeks. The hematocrit and the hemoglobin (Hb), blood urea nitrogen, plasma creatinine, and plasma erythropoietin levels were monitored.

Results: 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-Kyoto rats treated with 200 mg/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 mg/kg/day of adenine. Plasma erythropoietin concentrations were also not different between luseogliflozin- and vehicle-treated rats. Similarly, in human erythropoietin-producing cells derived from pluripotent stem cells, luseogliflozin treatment did not change the erythropoietin level in the medium.

Conclusions: These data suggest that SGLT2 inhibitor fails to exert hematopoietic effects in non-diabetic conditions.

Keywords:

Erythropoietin; Renal anemia; Sodium-glucose cotransporter 2 inhibitor

(医博甲751)

Author
著者 山﨑 大輔
著者(ヨミ) ヤマザキ ダイスケ
著者(別表記) yamazaki Daisuke
Publication Title
Journal of diabetes investigation
Publication Title Alternative
J Diabetes Investig.
Publisher
Asian Association for the Study of Diabetes
Wiley
Published Date
2019-12-27
ISSN
2040-1116
NCID
AA12488319
PMID
31880858
DOI
10.1111/jdi.13205
Resource Type
Thesis or Dissertation
Language
eng
Rights
Copyright © 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
"This is the Publisher's Version of the following article: Failure to confirm a sodium-glucose cotransporter 2 inhibitor-induced hematopoietic effect in non-diabetic rats with renal anemia; Journal of diabetes investigation; (2019) doi: 10.1111/jdi.13205, which has been published in final form at https://doi.org/10.1111/jdi.13205 . "
This Open Access article is licensed under the Creative Commons Attribution-NonCommercial 4.0 (CC BY-NC) International (https://creativecommons.org/licenses/by-nc/4.0/) License.
Text Version
ETD
Grant ID
博甲第751号
Grant Date
2020-06-25
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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