Details
| Original language | English |
|---|---|
| Pages (from-to) | 574-580 |
| Number of pages | 7 |
| Journal | Arzneimittel-Forschung/Drug Research |
| Volume | 58 |
| Issue number | 11 |
| Publication status | Published - Nov 2008 |
| Externally published | Yes |
Abstract
AVE2268, a substituted glycopyranoside, is an orally active and selective inhibitor of sodium-dependent glucose transporter 2 (SGLT2; IC50=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 (ID30 = 79 ± 8.1 mg/kg p.o.) and rats (ID30 = 39.8 ± 4.0 mg/kg p.o.). AVE2268 in mice was more potent to decrease blood glucose ascent when glucose was given intraperitoneally (ID50 = 13.2 ± 3.9 mg/kg), compared to orally administered glucose (ID50 = 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 (IC50 > 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.
Keywords
- Antidiabetic agents, AVE2268, effect on blood glucose, mouse, rat, Glucose, renal filtration, sodium-dependent glucose transporter 2, urinary excretion, Glycopyranoside, substituted, Phlorizin
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Drug Discovery
Sustainable Development Goals
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In: Arzneimittel-Forschung/Drug Research, Vol. 58, No. 11, 11.2008, p. 574-580.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Effects of AVE2268, a Substituted Glycopyranoside, on Urinary Glucose Excretion and Blood Glucose in Mice and Rats
AU - Bickel, Martin
AU - Brummerhop, Harm
AU - Frick, Wendelin
AU - Glombik, Heiner
AU - Herling, Andreas Waldemar
AU - Heuer, Hubert Otto
AU - Plettenburg, Oliver
AU - Theis, Stefan
AU - Werner, Ulrich
AU - Kramer, Werner
PY - 2008/11
Y1 - 2008/11
N2 - AVE2268, a substituted glycopyranoside, is an orally active and selective inhibitor of sodium-dependent glucose transporter 2 (SGLT2; IC50=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 (ID30 = 79 ± 8.1 mg/kg p.o.) and rats (ID30 = 39.8 ± 4.0 mg/kg p.o.). AVE2268 in mice was more potent to decrease blood glucose ascent when glucose was given intraperitoneally (ID50 = 13.2 ± 3.9 mg/kg), compared to orally administered glucose (ID50 = 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 (IC50 > 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.
AB - AVE2268, a substituted glycopyranoside, is an orally active and selective inhibitor of sodium-dependent glucose transporter 2 (SGLT2; IC50=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 (ID30 = 79 ± 8.1 mg/kg p.o.) and rats (ID30 = 39.8 ± 4.0 mg/kg p.o.). AVE2268 in mice was more potent to decrease blood glucose ascent when glucose was given intraperitoneally (ID50 = 13.2 ± 3.9 mg/kg), compared to orally administered glucose (ID50 = 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 (IC50 > 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.
KW - Antidiabetic agents
KW - AVE2268, effect on blood glucose, mouse, rat
KW - Glucose, renal filtration, sodium-dependent glucose transporter 2, urinary excretion
KW - Glycopyranoside, substituted
KW - Phlorizin
UR - http://www.scopus.com/inward/record.url?scp=57649135211&partnerID=8YFLogxK
U2 - 10.1055/s-0031-1296559
DO - 10.1055/s-0031-1296559
M3 - Article
C2 - 19137908
AN - SCOPUS:57649135211
VL - 58
SP - 574
EP - 580
JO - Arzneimittel-Forschung/Drug Research
JF - Arzneimittel-Forschung/Drug Research
SN - 0004-4172
IS - 11
ER -