AMG 837: A Novel GPR40/FFA1 Agonist that Enhances Insulin Secretion and Lowers Glucose Levels in Rodents
Figure 5
Efficacy of AMG 837 in Zucker fatty (fa/fa) rats following daily dosing for 21-days.
8-week old Zucker fatty rats were administered a single bolus of AMG 837 (at 0.03, 0.1 and 0.3 mg/kg, n = 6/group) by oral gavage 30-minutes prior to an intraperitoneal glucose challenge at t = 0 minutes. (A) Blood glucose during the IPGTT (black circle = vehicle, blue triangle = 0.03 mg/kg AMG 837, green diamond = 0.1 mg/kg AMG 837 and purple square = 0.3 mg/kg AMG 837). (B) Glucose AUC (from −30 to 120 minutes) during the IPGTT. (E) Plasma insulin levels during the IPGTT (black bar = vehicle, blue bar = 0.03 mg/kg AMG 837, green bar = 0.1 mg/kg AMG 837 and purple bar = 0.3 mg/kg AMG 837). Once daily dosing was continued for 21-days. On day 21, an IPGTT was performed in an identical manner to that on day 1. (C) Blood glucose (D) glucose AUC (from −30 to 120 minutes) and (F) plasma insulin levels were measured from the day 21 IPGTT. Figure legends are identical to those of the day 1 figures. (G) Body weights of the animals were followed through the course of the 21-day study; no difference in BW was observed between the groups. (H) Total plasma concentration of AMG 837 30-minutes following the final dose on day 21. Statistical significance compared to vehicle treated animals is denoted by * (p<0.5), ** (p<0.01) and *** (p<0.001) as determined by one-way or two-way ANOVA.