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 4
Hyperglucagonemia induced by GCGR ASO treatment is reversible. (A) Seven-week-old male db^+/? mice were treated twice per week (every 3.5 days) by subcutaneous injection with saline (filled squares), GCGR ASO 180475 (open circles), or control ASO 141923 (filled inverted triangles). ASOs were administered at 25 mg/kg for the first 9 doses and at 10 mg/kg for an additional 18 doses (last treatment on day 91) followed by a treatment-free washout period of 8 weeks. Nonfasted plasma glucose was measured every two weeks, and the data are expressed as the mean ± SEM of 8 mice per treatment group. (B) Nonfasted plasma glucagon was measured every two weeks from the animals described in (A), and the data are expressed as the mean ± SEM of 8 mice per treatment group. (C) GCGR mRNA was measured by real-time quantitative RT-PCR from the livers of 5 animals removed from the study at the time points indicated. Eukaryotic 18S ribosomal RNA was measured and used to normalize RNA input. Data are the mean values ± SEM of 5 mice per treatment group (P < 0.05 using the Student’s t test).