Hepatic and glucagon-like peptide-1–mediated reversal of diabetes by glucagon receptor antisense oligonucleotide inhibitors
J. Clin. Invest. Kyle W. Sloop, et al. 113:1571 doi:10.1172/JCI20911 [Go to this article.]

Figure 6
GCGR ASO treatment affects gluconeogenic and glycogenolytic enzyme gene expression and glycogen content in liver. (A) Expression of genes encoding gluconeogenic and glycogenolytic enzymes in GCGR ASO–treated SD rats. Real-time quantitative RT-PCR was used to profile gene expression from the livers of SD rats treated with GCGR ASO 180475 or saline for 4 weeks. Hepatic GCGR, glucose-6-phosphatase catalytic subunit (G-6-Pase [cat]), phosphoenolpyruvate carboxykinase, cytosolic isoform (PEPCK-C), fructose-1,6-bisphosphatase (F-1,6-Bpase), and glycogen phosphorylase (GP) mRNA levels showed significant differences when compared to control ASO–treated animals (P < 0.05 using the Student’s t test). Differences in the mRNA levels of GK and PPARγ were not observed. Rat 36B4 ribosomal phosphoprotein mRNA was measured and used to normalize RNA input. Data are the mean values ± SEM of 5 rats per treatment group. (B) Expression of genes encoding gluconeogenic and glycogenolytic enzymes in GCGR ASO–treated ZDF rats. Real-time quantitative RT-PCR was used to profile gene expression from livers of ZDF rats treated as described in (A). (C) Glycogen was measured as described in Methods in liver samples from 11-week-old db/db mice (n = 5 per treatment group), which had been treated twice per week (every 3.5 days) by subcutaneous injection with saline (black bar), GCGR ASO 180475 (white bar), or control ASO 141923 (gray bar) for 9 total doses. ASOs were administered at 25 mg/kg. GCGR ASO–treated mice had increased liver glycogen in the fasted state (P < 0.05) with no significant change in the fed state.