Figure 4.

Effect of 5-HT_2CR Agonists on Insulin Signaling

(A–C) A single injection of mCPP (1 mg/kg, i.p.) 45 min prior to insulin (0.5 U/kg, i.p.; gray bars) significantly increased Ser473 phosphorylation of PKB in liver (A) and skeletal muscle (B), but not white adipose tissue (WAT) (C), compared to saline treatment in 12 hr-fasted DIO mice (n = 30, mean body weight = 37 g). Representative western blots are displayed above each bar graph.

(D) Supporting a role for the MC4Rs in this effect, DIO WT and DIO Mc3r KO mice (n = 16, mean body weight = 42 g) treated with mCPP (1 mg/kg, i.p.; black bars) displayed a similar augmentation of insulin (0.5 U/kg, i.p.)-induced Ser473 phosphorylation of PKB in muscle compared to saline-treated counterparts (white bars), an effect absent in Mc4r KO mice.

(E and F) Moreover, prolonged treatment with mCPP (1 mg/kg/day for 7 days, s.c. minipump) significantly reduced PEPCK (E) and G6P (F) mRNA expression in the liver of DIO mice (n = 10, mean body weight = 36 g). AU, arbitrary units.

Data are presented as mean ± SEM. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.