Characterization of a Novel Glucokinase Activator in Rat and Mouse Models
Figure 3
GKA23 decreases hepatic glucose production.
(A) Glucose levels during the euglycemic hyperinsulinemic clamp study in control or GKA23 treated rats (n = 6/group). A bolus injection of GKA23 (30 mg/kg) was given i.p. at 30 min before insulin infusion. Glucose levels were clamped at 100 mg/dl. (B) Basal and clamped insulin levels in vehicle- and GKA23-treated mice. (C) Basal and clamped hepatic glucose production (HGP). (D) Glucose infusion rate (GIR) during the clamp study. (E) GIR at steady state in the final 20 minutes of the clamp study. (F) HGP suppression by insulin during the clamp study (G) Total glucose disposal rate (GDR). (H) Insulin-stimulated glucose disposal rate (IS-GDR) during the clamp study. (I) Glucose levels during the pyruvate tolerance test (PTT; 1 g/kg) on 6 hour-fasted rats (n = 6/group). Vehicle or GKA23 (30 mg/kg) was administered i.p. at −30 min and pyruvate was administered i.p. at 0 min. Statistical significance comparing vehicle and GKA23 is expressed as *P<0.05, **P<0.01, ***P<0.001, and ****P<0.0001. NS, not significant.