Effects of acute GIPR antagonism on glucose homeostasis and insulin secretion.

GIPA-1 and GIPA-2 are antagonists of mouse GIPR. Plots (A and B) shows the inhibition of mouse GIPR by GIPA-1 (A) and GIPA-2(B) in CHO-K1 cells. IC₅₀ values (μM) are indicated on the plots. (C-J) Acute effects of GIPA-1 and GIPA-2 on glucose homeostasis and insulin secretion in lean mice. Oral glucose tolerance tests (C and E), the corresponding areas under the curve (AUC) (D and F) and insulin responses (I) following subcutaneous injections of vehicle, 1,5 and 10 mg/kg GIPA-1 (C and D) or vehicle, 1,5 and 10 mg/kg GIPA-2 (E and F) before an oral glucose administration (1.5 g/kg). (G, H and J) Acute effect of GIPA-2 alone or in combination with mouse GIP on glucose homeostasis and insulin secretion in lean mice. Intraperitoneal glucose tolerance test cute IPGTT (G), the corresponding AUC (H) and insulin response (J) following subcutaneous injections of vehicle, 0.1 mg/kg mouse GIP, 5mg/kg GIPA-2, and combination of both. Group sizes are n = 8, and data are represented as mean ± SEM. Statistical analysis was calculated using two-way ANOVA with Tukey’s post-hoc test (C, E, G and J) and one-way ANOVA with Dunnett’s post-hoc test (D, F, H, I). *: p< 0.05, **: p < 0.01, ***: p < 0.001, ****: p<0.0001 compared to vehicle.