The insulin-induced ET-1–dependent contraction is suppressed in APPL1-Tg mice on HFD. A: Effect of insulin in mesenteric arteries of 16-week-old WT mice on HFD in the presence of the ERK1/2 inhibitor PD98059 (5 μmol/L) or the ET-1A receptor antagonist BQ123 (1 μmol/L). Data are expressed as percentage of the contraction to U46619. B: Effect of insulin in mesenteric arteries of 16-week-old APPL1-Tg and WT mice fed HFD or STD in the presence of l-NAME (100 μmol/L). Data are shown as area under the curve (AUC). C: The mRNA levels of ET-1 in mesenteric arteries from 16-week-old APPL1-Tg and WT mice fed STD or HFD were quantified by real-time quantitative-PCR and normalized against GAPDH. *P < 0.05, **P < 0.01 (n = 5–8).