Effects of AVE2268, a substituted glycopyranoside, on urinary glucose excretion and blood glucose in mice and rats
Arzneimittel-Forschung/Drug Research, ISSN: 0004-4172, Vol: 58, Issue: 11, Page: 574-580
2008
- 25Citations
- 14Captures
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Metrics Details
- Citations25
- Citation Indexes25
- 25
- CrossRef1
- Captures14
- Readers14
- 14
Article Description
AVE2268, a substituted glycopyranoside, is an orally active and selective inhibitor of sodium-dependent glucose transporter 2 (SGLT2; IC=13 nmol/L). Investigation of the pharmacological profile of AVE2268 on urinary glucose excretion (UGE) and blood glucose after glucose challenge (po or intraperitoneal) was performed in mice and rats. AVE2268 caused a dose-dependent increase of UGE in mice (ID = 79 ± 8.1 mg/kg p.o.) and rats (ID = 39.8 ± 4.0 mg/kg p.o.). AVE2268 in mice was more potent to decrease blood glucose ascent when glucose was given intraperitoneally (ID = 13.2 ± 3.9 mg/kg), compared to orally administered glucose (ID = 26.1 ± 3.9 mg/kg), showing that AVE2268 has no effects on SGLT 1 in the gut in vivo, which is in accordance with ist very low affinity to the SGLT 1 in vitro (IC > 10,000 nmol/L). During an oral glucose tolerance test, AVE2268 dose-dependently increased UGE, with subsequent decreases of AUC and blood glucose. A highly significant inverse correlation between AUC and UGE was found (p<0.001).The increase in UGE is linked to the inhibition of SGLT2 only. This profile renders AVE2268 as a new antidiabetic drug for the treatment of type 2 diabetes. © ECV Editio Cantor Verlag.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=57649135211&origin=inward; http://dx.doi.org/10.1055/s-0031-1296559; http://www.ncbi.nlm.nih.gov/pubmed/19137908; http://www.thieme-connect.de/DOI/DOI?10.1055/s-0031-1296559; https://dx.doi.org/10.1055/s-0031-1296559; https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0031-1296559
Georg Thieme Verlag KG
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