Biological Activity
as 1269574,(2-[2-(4-bromophenyl)-6-methylpyrimidin-4-yl] amino ethanol), was capable of inducing glucose-stimulated insulin secretion (gsis) and improved glucose tolerance in normal mice. as 1269574 is an agonist of gpr119 with ec50 value of 2.5 μm [1] [2].gpr119 is highly expressed in pancreatic β-cells. this receptor enhances the effect of gsis via the elevation of intracellular camp concentrations [2].treated with either 1 or 10 μm as 1269574 for 20 min, the insulin secretion of mouse pancreatic min-6 β-cells pre-exposed to 16.8 mm glucose was significantly increased compared with the dmso vehicle control. in contrast, as 1269574 did not affect the insulin release of min-6 cells previously treated with low-glucose (2.8 mm) [2].in normal mice, a single treatment with 100 mg/kg of as 1269574 significantly reduced the area under the curve (auc) after 2 h (auc0-2h) of blood glucose. as 1269574 significantly increase the plasma insulin auc0-2h in mice compared with the vehicle control. a single oral administration of 100 mg/kg as 1269574 did not significantly lower the blood glucose auc in either fasted or fed mice, indicating as 1269574 did not have a hypoglycemic effect [2].
References
[1]. shigeru yoshida, hirotsugu tanaka, hiroyuki oshima, et al. as1907417, a novel gpr119 agonist, as an insulinotropic and β-cell preservative agent for the treatment of type 2 diabetes. biochemical and biophysical research communications, 2010, 400: 745-751.
[2]. shigeru yoshida, takahide ohishi, tetsuo matsui, et al. identification of a novel gpr119 agonist, as1269574, with in vitro and in vivo glucose-stimulated insulin secretion. biochemical and biophysical research communications, 2010, 400: 437-441.
