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Pharmacological Characterization of YM543, a Newly Synthesized, Orally Active SGLT2 Selective Inhibitor. | LitMetric

AI Article Synopsis

Article 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/A 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.

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Source
http://dx.doi.org/10.3109/07435800.2012.746364DOI Listing

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