Leptin reverses STZ-induced diabetes in a dose-dependent manner. Mice were treated with STZ and 6 days later received implantation
of osmotic pumps (day 0, vertical broken line) delivering doses of either leptin ranging from 1 to 10 µg/day (STZ and 1, 3,
5, or 10 µg/day) or vehicle only (STZ-vehicle). Nondiabetic mice served as controls. Fasting blood glucose (A) and change in body weight (B) relative to day −1. AUC analysis of blood glucose levels from day 5 to day 12 is presented (A). AUC analysis of body weight change from day 5 to day 12 revealed no significant differences and is not shown. C: The 4-h fasted plasma insulin levels on day 25. Limit of detection is shown by broken horizontal line. D: The 4-h fasted plasma leptin levels on days 12 and 25. Four of five STZ-vehicle mice had leptin levels below the detection
limit (indicated by broken line) on both days, and this group was not included in statistical analyses. Statistical analyses
were performed by two-way ANOVA with Tukey post hoc test. E: The 4-h fasted plasma IGFBP2 levels on day 12. Data are presented as mean ± SEM, n = 4–5. *P < 0.05. †P < 0.05 vs. nondiabetic controls. ‡P < 0.05 vs. STZ-vehicle controls.