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. 2006 Feb 16;116(3):817–824. doi: 10.1172/JCI27300

Figure 5.

Figure 5

Acc1 and -2 ASO therapy improves hepatic insulin signaling. Acc1 and -2 ASO treatment does not alter basal HGP (A) but enhances insulin-mediated suppression of HGP in high-fat–fed rats (B). Reduced PKCε membrane translocation (C) may be directly involved in improving hepatic insulin signaling. This change is associated with increased Akt2 activity (D) and increased Foxo1 phosphorylation, which promotes nuclear exclusion of Foxo1, thereby lowering its transcriptional activity on the promoters of gluconeogenic genes, such as PEPCK and G6P. (D) Akt2 activity before (basal) and after 20 minutes insulin stimulation in ASOctrl and Acc1 and -2 ASO–treated rats. (E) Foxo1 phosphorylation was assessed before (basal) and after 20 minutes insulin stimulation by Western blotting using an antibody specific for serine256 phosphorylation. Data is expressed as the ratio of phosphorylated Foxo1 (Phos-Foxo1)/actin (loading control). (F) Suppression of hepatic PEPCK mRNA and (G) G6P mRNA expression during hyperinsulinemic-euglycemic clamps. *P < 0.05 versus ASOctrl treatment group. Data are expressed as mean values ± SEM for 4–6 rats per treatment group. *P < 0.05 versus ASOctrl treatment group.