AMG 837: A Novel GPR40/FFA1 Agonist that Enhances Insulin Secretion and Lowers Glucose Levels in Rodents
Figure 3
Improvement in glucose tolerance and potentiation of insulin secretion in Sprague-Dawley rats treated with AMG 837.
8-week old Sprague-Dawley rats were treated with 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 measurements were taken during prior to and following glucose challenge. 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) The glucose AUC (from −30 to 120 minutes) during the course of the experiments were calculated. (C) Plasma insulin levels were measured using ELISA. 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 (D–D) Two successive glucose challenges were conducted in Sprague-Dawley rats following a single oral dose of vehicle (n = 4, black circle) or AMG 837 at 0.3 mg/kg (n = 4, purple diamond). AMG 837 was dosed at −30 minutes, and glucose was administered by ip injection at 0 and 180 minutes. Blood glucose (D), calculated glucose AUC (from 0–60 minutes following glucose challenge (E, black bars = vehicle, purple bars = 0.3 mg/kg AMG 837) and plasma insulin (F) were determined. Statistical significance is denoted by * (p<0.5), ** (p<0.01) and *** (p<0.001) as determined by one-way or two-way ANOVA.