Figure 7. The intraperitoneal glucose tolerance test (A) and insulin tolerance test (B) were performed in DIO mice treated with HIF-1α ASO, control ASO or observed untreated.

The hyperinsulinemic euglycemic clamp was performed in HIF-1α ASO treated and untreated mice (C, D). The baseline hepatic glucose output (C) was determined as the ratio of the [³H] glucose infusion rate to the specific activity of plasma glucose prior to the clamp. The hepatic glucose output during the clamp was determined as the difference between the ratio of the [³H] glucose infusion rate to the specific activity of plasma glucose and non-radioactive glucose infusion rate during last 30 min of the clamp. The whole body insulin sensitivity (D) was measured by glucose infusion rate during last 30 min of hyperinsulinemic euglycemic clamp (glucose levels were clamped at 100–125 mg/dl). * denotes p<0.001 for the difference between untreated or control ASO treated and HIF-1α ASO treated mice; † denotes p<0.001 for the difference between untreated and control ASO treated mice; ‡ denotes p<0.05 for the difference between untreated and HIF-1α ASO treated mice.