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 2
Time course analysis of GCGR mRNA reduction and plasma glucose lowering in ZDF rats. (A) Liver GCGR mRNA reduction in ZDF rats. Seven-week-old male ZDF rats were treated twice per week (every 3.5 days) by subcutaneous injection with control ASO 141923 (filled inverted triangles) or GCGR ASO 180475 (open circles) at 25 mg/kg for 9 doses (last treatment on day 28) followed by a washout period of equal duration. GCGR mRNA was measured by real-time quantitative RT-PCR from livers of 5 animals removed from the study at each time point. Eukaryotic 18S ribosomal RNA was measured and used to normalize RNA input. Data are the mean values ± SEM of five rats per treatment group. In overall comparisons during the treatment period, target reduction by GCGR ASO 180475 was significantly different when compared with that in control ASO–treated animals (P < 0.05 adjusted using Tukey's t test). (B) Nonfasted plasma glucose in ZDF rats treated as described in (A). Data are the mean values ± SEM of five rats per treatment group. In overall comparisons during the treatment period, glucose-lowering by GCGR ASO treatment showed significant differences when compared with that in control ASO–treated animals (P < 0.05 adjusted using Tukey's t test). (C) Nonfasted plasma insulin in ZDF rats treated as described in (A). Data are the mean values ± SEM of five rats per treatment group. No significant changes were observed during the treatment period; however, individual comparisons between GCGR ASO– and control ASO–treated animals on days 38 and 56 (washout period) were significant (P < 0.05).