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. 2022 Oct 28;66:101624. doi: 10.1016/j.molmet.2022.101624

Figure 4.

Figure 4

Gut FoxO1 ablation reverses hyperglycemia in INS2Akita/+. (A) Blood glucose levels in INS2Akita/+ mice with or without FoxO1fl/fl and VFKO alleles (n = 14–20 in each group). (B) Blood glucose levels in INS2Akita/+ and INS2Akita/+VFKO mice at 16–24 weeks ages after 4-hr fast, followed by 1-hr refeeding (n = 5 in each group). (C) Plasma insulin levels in INS2Akita/+ and INS2Akita/+VFKO mice at 8, 10, and 12 weeks ages (n = 6 in each group). (D–E) Oral glucose (1  g/kg glucose infusion) tolerance tests (OGTT) after 16-hr fast of INS2Akita/+ (white circles) and INS2Akita/+VFKO mice (red circles) following administration of vehicle (D) or GLP-1 antagonist, exendin-9 by i.p. (E) (n = 6 and 7 in each group). (F) Area under the curve (AUC) measurements of OGTT in (D) and (E). (G–L) Immunohistochemistry of GLP-1 (G–H), GIP (I–J), and C-peptide (K–L) in ileum (G–H), or duodenum (I–L) of INS2Akita/+ (G, I, and K) and INS2Akita/+VFKO mice (H, J, and L). VFKO, Vil-Cre (+); FoxO1fl/fl: Akita-WT, INS2Akita/+; FoxO1fl/fl: Akita-VFKO, INS2Akita/+; Vil-Cre (+): FoxO1fl/fl. Data are presented as means ± SD. Scale bar = 50 μm, DAPI counterstains nuclei. ∗ = p < 0.05; ∗∗ = p < 0.01; ∗∗∗ = p < 0.001 by two-factor ANOVA.