Figure 3.

Effects on hepatic gluconeogenesis, insulin sensitivity, and glucose tolerance in mice treated acutely with EGF alone or chronically in HFD-fed mice exposed to $\text{Aroclor\hspace{0.17em}}1260\pm \text{EGF}$ treatment. Male WT C57Bl/6 mice fed a control diet were treated with either saline or EGF at multiple doses (0.002, 0.02, $0.2\mathrm{\mu }\mathrm{g}/\mathrm{g}$), followed by euthanasia at 30 min post IP injection, and tissue was harvested for downstream analysis. Male WT C57Bl/6 mice were fed an HFD (12 wk) and exposed to either vehicle or Aroclor 1260 ($20\mathrm{mg}/\mathrm{kg}$) by a one-time oral gavage at week 1. Aroclor 1260-exposed or vehicle mice were treated (via IP injection) with saline or EGF ($0.2\mathrm{mg}/\mathrm{g}$) daily for 10 d starting at week 10. Mice were fasted for 12 h and euthanized, and tissues were harvested for downstream analyses. (A) Plasma glucose (Ai) and plasma pyruvate (Aii) were measured in mice treated with EGF (0.002, 0.02, $0.2\mathrm{\mu }\mathrm{g}/\mathrm{g}$) or saline control for 30 min (acute). (B) Plasma glucose (Bi) and plasma pyruvate (Bii) were measured in mice gavaged with corn oil and injected with either saline (CS) or EGF ($0.2\mathrm{\mu }\mathrm{g}/\mathrm{g}$) (CE) or gavaged with Aroclor 1260 ($20\mathrm{mg}/\mathrm{kg}$) and injected with saline (AS) or EGF (AE) at the conclusion of the chronic model (12 wk). (Ci-ii) GTTs were performed in the CS, CE, AS, and AE mice as well as (Di-ii) ITTs. An $n=5$ was used for Figures 3Ai–ii, and the red dot is the $\text{mean}\pm \text{SEM}$ for saline controls for Figures 3Ai–ii. An $n=17$ was used for Figures 3B–D. A two-way ANOVA was used to statistically compare data sets, followed by a Sidak correction for intergroup comparisons. A $p<0.05$ was considered significant. Significance due to EGF is denoted by (a); Aroclor 1260 denoted by (b); and due to interaction denoted by (c) for the two-way ANOVA. A $p<0.05$ was denoted by * for the Sidak multiple comparison test. Data are represented as $\text{mean}\pm \text{SEM}$ for Figures 3Ai, 3Aii, 3Ci, and 3Di, but data are presented as box and whisker plots for Figures 3Bii, 3Cii, and 3Dii that illustrate the median (midline), upper and lower quartiles (box), and the upper and lower limits (whiskers). All numerical data are presented in Table S6 “Numerical Data” as $\text{mean}\pm \text{SD}$, and p-values can be found in Table S5. Numeric outliers were identified by ROUT method and removed. The number of outliers are reported in Table S4. Note: AE, $\text{Aroclor\hspace{0.17em}}1260+\text{EGF}$; ANOVA, analysis of variance; AS, $\text{Aroclor\hspace{0.17em}}1260+\text{saline}$; CE, $\text{control}+\text{EGF}$; CS, $\text{control}+\text{saline}$; EGF, epidermal growth factor; GTT, glucose tolerance test; HFD, high-fat diet; IP, intraperitoneal; ITT, insulin tolerance test.