Figure 1. Rap1 mediates hyperglycemia in the hypothalamus.

(A and B) Increased hypothalamic Rap1 activity aggravates hyperglycemia under HFD conditions. Body weight (A) and blood glucose (B) of Rap1^V12 mice are shown. Six weeks after AAV-Rap1^V12 injection, mice were subjected to HFD feeding (n = 12/group). (C and D) Hypothalamic deletion of Rap1a and Rap1b prevents HFD-induced hyperglycemia. Shown are the body weight (C) and blood glucose (D) of Rap1^ΔHYP mice. One week after AAV2-Cre injection into the medial hypothalamus of the Rap1a and Rap1b double-floxed mice, HFD feeding started (n = 12–13/group). Values are presented as the mean ± SEM. ^#P < 0.05, ^##P < 0.01, and ^###P < 0.001 compared with each group on day 0, by 1-way ANOVA followed by Dunnett’s multiple comparisons test, and *P < 0.05, **P < 0.01, and ***P < 0.001 compared with the control group, by repeated measures 2-way ANOVA with Bonferroni’s multiple comparisons test.