The G-protein coupled receptor 40 (GPR40) mediates both acute and chronic effects of FFAs (free fatty acid) on insulin secretion and plays an important role in glucose homeostasis. DC260126 is a small-molecule GPR40 antagonist. In db/db mice, the FSI (fasting serum insulin) level was decreased dose-dependently after giving different dose of DC260126 for 5 days. Both 10 and 30 mg/kg DC260126 could reduce FSI level of db/db mice significantly. Further, DC260126 could lower fasted serum insulin levels and alter glucose-stimulated insulin secretion in db/db mice. In DC260126 treated db/db mice, insulin expression was decreased in islet compared with vehicle treated mice. Moreover, DC260126-treated mice showed an obvious decrease of blood glucose levels during ITT in response to insulin compared to the vehicle-treated group. Lastly, the phase 2 of glucose-stimulated insulin secretion was obviously suppressed in DC260126-treated db/db mice in comparison with vehicle group[3]. Also, DC260126 could protect MIN6 β cells from palmitate-induced ER stress and apoptosis Wu J, Sun P, Zhang X, Liu H, Jiang H, Zhu W, Wang H. Inhibition of GPR40 protects MIN6 β cells from palmitate-induced ER stress and apoptosis. J Cell Biochem. 2012 Apr;113(4):1152-8. doi: 10.1002/jcb.23450. Erratum in: J Cell Biochem. 2013 May;114(5):1216.
DC260126 细胞实验
Cell Line
Concentration
Treated Time
Description
References
pancreatic acinar AR42J cells
10 μM
2 h
DC260126 suppressed the inhibitory effect of DHA on cerulein-induced zymogen activation
Genes Nutr. 2020 Mar 23;15(1):6.
DC260126 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Db/db mice
Obese diabetic model
Tail vein injection
10 mg/kg
Once daily for 21 days
DC260126 significantly inhibited glucose stimulated insulin secretion, reduced blood insulin level and improved insulin sensitivity. Moreover, DC260126 reduced the proinsulin/insulin ratio and the apoptotic rate of pancreatic β-cells remarkably.
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