GCGR ASO therapy improves pancreatic β cell function. (A) An intraperitoneal glucose challenge (2 g glucose/kg body wt) was performed on 9-week-old male SD rats (n = 5 per treatment group), which had been treated twice per week (every 3.5 days) by subcutaneous injection with saline (filled squares) or GCGR ASO 180475 (open circles) for 8 doses. ASOs were administered at 25 mg/kg. Blood samples were taken at the indicated time points, and plasma glucose levels were determined. Results are expressed as mean ± SEM. Inset depicts the log of the area under the glucose excursion curve (AUC) for saline (black bar) and GCGR ASO (white bar). P < 0.05. (B) Plasma insulin levels for the indicated time points during the glucose challenge described in (A). Results are expressed as mean ± SEM. Inset depicts the log of the area under the insulin excursion curve for saline (black bar) and GCGR ASO (white bar). P < 0.05. (C) An intraperitoneal glucose challenge (2 g glucose/kg body wt) was performed on 15-week-old male ZDF rats (n = 5 per treatment group), which had been treated as described in (A). Results are expressed as mean ± SEM. Inset depicts the log of the area under the glucose excursion curve for saline (black bar) and GCGR ASO (white bar). P < 0.05. (D) Plasma insulin levels for the indicated time points during the glucose challenge described in (C). Results are expressed as mean ± SEM. Inset depicts the log of the area under the insulin excursion curve for saline (black bar) and GCGR ASO (white bar). P < 0.05.