Fig. 4.

Effect of HFD on glucagon and insulin in WT and ACE2 KO mice. A: HFD-fed WT mice had significantly lower-glucagon mRNA levels, while ACE2 KO mice on HFD had significantly higher levels in the islets. HFD feeding significantly increased plasma insulin levels (B) and elevated insulin/glucagon gene expression ratio (C) in WT mice but significantly decreased plasma insulin levels (B) and insulin/glucagon gene expression ratio (C) in ACE2 KO mice. D: ex vivo treatment with normal (5 mM) and high (25 mM) glucose concentrations in the presence and absence of 100 nM ANG II and ANG-(1–7) for 3 h showed no effect on glucagon mRNA levels in isolated islets of WT mice. Statistical significance, *P < 0.05, **P < 0.01 vs. WT RD; $$P < 0.01 vs. ACE2 KO RD; #P < 0.05, ##P < 0.01, ###P < 0.001 vs. WT HFD using two-way ANOVA followed by Bonferroni’s multiple comparison test.