Figure 12. Treatment with pNAPE-EcN preserves insulin sensitivity in liver by protecting against inhibitory phosphorylation of IRS1 by JNKs.

Mice treated with standard water only (W), with pEcN (E), or with pNAPE-EcN (N) for 6 weeks were fasted for 4 hours and then injected intraperitoneally with either saline (to determine response to endogenous levels of insulin; n = 5 mice per group) or 0.75 IU/kg insulin (to determine response to exogenous, pharmacological levels of insulin; n = 4–5 mice per group). 15 minutes after injection, mice were euthanized and tissue collected. Data are the mean ± SEM. (A) Extent of activating phosphorylation of Ser473 of AKT (p-AKT) in liver of saline-injected mice. Values were normalized to plasma insulin (INS) and expressed relative to the average for water-only–treated mice. P = 0.0225 by 1-way ANOVA; *P < 0.05 versus standard water by Dunnett’s multiple comparison test. (B) Extent of inhibitory Ser307 phosphorylation of IRS1. Values were normalized to heat shock protein (HSP) and expressed relative to the average for standard water-only–treated mice. P = 0.0173 by 1-way ANOVA; *P < 0.05 versus standard water by Dunnett’s multiple comparison test. (C) Extent of activating phosphorylation of JNK isoforms p46 and p54. Values were normalized to HSP and expressed relative to the average for standard water-only–treated mice. For p46-JNK, P = 0.0084 by 1-way ANOVA; *P < 0.05 versus standard water by Dunnett’s multiple comparison test. For p54-JNK, P = 0.0134 by 1-way ANOVA; *P < 0.05 versus standard water by Dunnett’s multiple comparison test. There were no significant differences between groups stimulated with the exogenous insulin.