Pharmacological Characterization of YM543, a Newly Synthesized, Orally Active SGLT2 Selective Inhibitor.
Endocr Res
; 38(3): 168-183, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23374077
ABSTRACT
BACKGROUND AND AIM:
Sodium-glucose cotransporter (SGLT) 2 is a specifically expressed transporter in the kidney that plays an important role in renal glucose reabsorption, and its inhibition may present a novel therapeutic strategy for treating diabetes. Here, we pharmacologically characterized YM543, a newly synthesized SGLT2 selective inhibitor to test this theory.RESULTS:
In vitro studies revealed that YM543 potently and selectively inhibited mouse and human SGLT2 activities at nanomolar ranges. In vivo single oral administration of YM543 dose-dependently and significantly reduced blood glucose levels and improved glucose tolerance with a concomitant increase in urinary glucose excretion in KK/Ay type 2 diabetic mice, effects that were sustained even after 12 h. Repeated once-daily oral administration of YM543 for 5 weeks significantly reduced hyperglycemia in type 2 diabetic mice. In addition, combination treatment of YM543 with rosiglitazone or metformin additively improved diabetic symptoms. In contrast, YM543 did not affect normoglycemia at pharmacological doses in normal mice.CONCLUSIONS:
Results from the present study suggest that YM543 is an orally active SGLT2 selective inhibitor which reduces hyperglycemia with a concomitant increase in urinary glucose excretion, indicating its promise as an effective treatment against type 2 diabetes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Endocr Res
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão