Insulin and glucose tolerance test for H3^+/+ mice (squares) and H3^–/– mice (triangles). (a) Insulin tolerance test. Insulin was injected intraperitoneally into 26- to 28-week-old, 3-hour fasted female mice. Blood glucose levels were determined at the indicated times (n = 4–6, *P < 0.05; **P < 0.01). (b) Glucose tolerance test. Glucose was injected intraperitoneally into 26- to 28-week-old, 14-hour fasted female mice. Blood glucose levels were determined at the indicated times (n = 4–6, *P < 0.05). (c) Leptin sensitivity test. Leptin was injected intracerebroventricularly into 18- to 34-week-old male mice, and 24-hour food intake was determined (n = 5, *P < 0.05). White bars indicate saline and black bars leptin.