Figure 4.
RO5527239 improves glucose tolerance in mice and promotes GLP-1 secretion. (A) Oral glucose tolerance test (2 g·kg−1 glucose) in male 12-week-old GPBAR1-KI mice treated with vehicle (▵), or RO5527239 (30 mg·kg−1; ▴). Animals were first dosed with compound or vehicle 60 min before glucose bolus. Data represent the mean ± SEM. The inset represents the average delta AUC during 2 h (mean ± SD) (n = 8 per group). (B) Corresponding plasma total GLP-1 levels in GPBAR1-KI mice during an p.o. glucose challenge, 60 min after the p.o. administration of saline or RO5527239 (30 mg·kg−1). Data represent the mean ± SEM. (n = 8 per group). (C) Oral glucose tolerance test in male 8-week-old db/db mice using 1 g·kg−1 glucose treated concomitantly with vehicle (▵), RO5527239 (30 mg·kg−1; ▴), or preceded 60 min before by p.o. administration of sitagliptin (10 mg·kg−1; ○) alone, and in combination with RO5527239 (30 mg·kg−1; ♦). Data represent the mean ± SEM. (n = 8 per group). (D) Corresponding active GLP-1 plasma levels and (E) total GLP-1 plasma levels 2 h after glucose challenge. Data represent the mean ± SEM (n = 5 per group). Statistically significant: *P < 0.05; **P < 0.01, ***P < 0.001. Unpaired t-test (Figure 4A), anova followed by Dunnett's test (Figure 4C–E).