Figure 6.

Pharmacological inhibition of Foxo1 and Notch in AKITA^Ins2/+ mice. Mice were treated with vehicle, Cpd10 (50 mg/kg/), or PF-03084014 (150 mg/kg) or Cpd10 (50 mg/kg) + PF-03084014 (150 mg/kg) for 5 days. (A) Body weight measured before morning dosing. (B) Glucose levels measured around 5 pm on day 1 and day 4. N = 6–13 per group. (C) Oral glucose tolerance (OGTT) test. 2  g/kg of glucose solution was administered orally after a 4-hr fast. (D) Total AUC. (E) Plasma insulin levels at 0 and 20 min after arginine injection. (F) Gene expression in isolated epithelial cells for the markers indicated. N = 4–5 per group. (G–O) Representative intestinal immunohistochemistry after 10-day treatment and quantified data. Insulin (red) and 5-HT (green) (G–H), PC2 (red) and 5-HT (green) (I–J), C-peptide (K–L) and GLP-1 (red) and 5-HT (green) (L, M) staining of vehicle group (left panel, G, I, K, and N) and Cpd10/PF-03084014-treated group (right panel, H, J, L, O). Insulin⁺ and 5HT⁺, PC2⁺ and 5HT⁺, C-peptide⁺, GLP-1⁺, and 5HT⁺ cells quantification in villi and crypts (M). Data are presented as means ± SEM. Scale bar = 50 μm ∗ = p < 0.05; ∗∗ = p < 0.01; ∗∗∗ = p < 0.001; ∗∗∗∗ = p < 0.0001; NS: not significant. Two-way ANOVA was performed for (B), (E), (N), and (O). One-way ANOVA was performed for (D).