| Description: |
DC260126, a small-molecule antagonist of GPR40. |
| In Vitro: |
DC260126 is a small-molecule antagonist of GPR40 that protects against pancreatic β-cells dysfunction in db/db mice. After giving different dose of DC260126 to nine-week-old db/db mice for 5 days, the fasting serum insulin (FSI) level is decreased dose-dependently. And both 10 mg/kg and 30 mg/kg body weight can reduce FSI level of db/db mice significantly[1]. DC260126, a small-molecule antagonist of GPR40, is evaluated the effect of on glucose and lipid metabolism in obese Zucker rats. Rats are treated intraperitoneally with 6 mg/kg of DC260126 for 8 weeks. DC260126 treatment significantly decreases serum insulin levels by about 20% (147.5±10.42 versus 182.36±7.22, p<0.05). DC260126 treatment causes an elevation of body weight gain from 3 to 6 weeks compared with the vehicle-treated group. Compared with the vehicle-treated group, DC260126 treatment induces a significant increase of Akt phosphorylation levels in liver as assessed by western blotting[2]. |
| Animal Administration: |
Mice[1] Male C57BL/KsJ-Lepdb (db/db) are maintained in a 12 h light-dark cycle at a temperature of 23°C with free access to water and regular chow diet. To investigate the dose-dependent effect of DC260126, nine-week-old db/db male mice are divided into four groups (n=6/group). Mice are give vehicle (5% DMSO in PBS) or DC260126 (3, 10, 30 mg/kg) once daily by tail vein injection for 5 days. At day 5, each group of mice are fasted for 6 h and blood samples are collected from orbital venous plexus and centrifuged for serum separation. Then the concentration of serum insulin level is measured by ELISA kit. For long term experiments, six-week-old obese db/db male mice are divided into two groups (n=8/group) and given vehicle (5% DMSO in PBS) or DC260126 (10 mg/kg) once daily by tail vein injection for 24 days, respectively. Rats[2] Female obese (fa/fa) Zucker rats are maintained in a 12:12 light-dark cycle with free access to water and a high-fat diet containing 15% fat, 1% cholesterol, 0.5% sodium cholate and 15% sucrose, except when fasted before some experiments. Rats at 8 weeks of age are divided into two groups (n=6/group) on the basis of body weight. Rats are injected intraperitoneally once daily with vehicle (propylene glycol) or DC260126 (6 mg/kg) for 8 weeks. Food intake and body weight are monitored periodically. At the end of the experimental period, mice are fasted for 12 h and then blood is collected. Liver, renal, adipose tissues are rapidly excised and weighed. Liver samples are snap frozen in liquid nitrogen and stored at -80°C for western blotting analysis. |
| References: |
[1]. Sun P, et al. DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice. PLoS One. 2013 Jun 11;8(6):e66744.
[2]. Zhang X, et al. DC260126, a small-molecule antagonist of GPR40, improves insulin tolerance but not glucose tolerance in obese Zucker rats. Biomed Pharmacother. 2010 Nov;64(9):647-51. |
