Rax-CreERT2:ArcPomcloxTB/loxTBmice show significantly improved glucose tolerance and insulin sensitivity compared to ArcPomcloxTB/loxTBmice in response to an oral glucose tolerance test. (A, I) Blood glucose levels before fasting in male and female mice, measured using a glucometer. There was no significant difference in nonfasting blood glucose levels between the groups for either sex. (B, J) Plasma insulin levels before fasting in male and female mice, measured by ELISA. Rax-CreERT2/+:ArcPomcloxTB/loxTB male mice show lower nonfasting plasma insulin levels (∗p = 0.024; Tukey's multiple comparisons) compared to ArcPomcloxTB/loxTB mice. (C, K)Rax-CreERT2:ArcPomcloxTB/loxTB male, but not female, mice show significantly reduced blood glucose levels at 15 (∗∗p = 0.001, Tukey's multiple comparisons) and 30 min (∗p = 0.023, Tukey's multiple comparisons) after oral glucose challenge, compared to ArcPomcloxTB/loxTB mice. (D, L)Rax-CreERT2:ArcPomcloxTB/loxTB male, but not female, mice show significantly reduced plasma insulin levels at 0 (∗p = 0.024, Tukey's multiple comparisons), 60 (∗p = 0.023, Tukey's multiple comparisons), and 120 min (∗∗p = 0.006, Tukey's multiple comparisons) after oral glucose challenge, compared to ArcPomcloxTB/loxTB mice. (E, M)Rax-CreERT2:ArcPomcloxTB/loxTB male, but not female mice, show significantly reduced glucose areas under the curve (AUC; ∗p = 0.023, Tukey's multiple comparisons) compared to ArcPomcloxTB/loxTB mice. (F, N)Rax-CreERT2:ArcPomcloxTB/loxTB male and female mice show significantly reduced insulin areas under the curve (AUC; male: ∗p = 0.012, female: ∗∗p = 0.006; Tukey's multiple comparisons) compared to ArcPomcloxTB/loxTB mice. (G, O)Rax-CreERT2:ArcPomcloxTB/loxTB male and female mice show significantly reduced glucose-insulin indexes (male: ∗∗p = 0.007, female: ∗p = 0.014; Tukey's multiple comparisons). (H, P)Rax-CreERT2:ArcPomcloxTB/loxTB male, but not female, mice show significantly reduced HOMA-IR indexes (∗p = 0.047, Tukey's multiple comparisons) compared to ArcPomcloxTB/loxTB mice. Data are shown as mean ± SEM (males, n = 6–9/group; females, n = 3–8/group). Individual mouse values are represented by filled circles. The data were analyzed using one-way ANOVAs followed by Tukey's multiple comparisons test.