FIG. 5.

In vivo administration of the ERβ agonist (WAY200070) improved glucose tolerance in mildly diabetic mice and restored plasma insulin levels and pancreatic β-cell mass. A: Mild diabetes was induced by the administration of a single dose of STZ 150 mg/kg and NA 1,000 mg/kg. Ten days after the treatment, these animals exhibited moderate hyperglycemia and impaired glucose tolerance compared with controls (8–15 mice/group). The AUC in these mice was significantly increased (inset). *P < 0.05 versus control (Student t test). B: At this point, 1-week treatment with the ERβ agonist resulted in a decrease of fasting glycemia as well as a better sensitivity to a glucose challenge in the W10 diabetic group compared with the vehicle-treated diabetic group (7–8 mice/group). *P < 0.05 diabetic vehicle vs. diabetic W10; #P < 0.05 diabetic vehicle vs. control. C: Plasma insulin levels in diabetic mice treated with WAY200070 during 1 week compared with control and nontreated diabetic mice. We observed that levels of plasma insulin in treated diabetic mice were similar to controls; meanwhile, levels in diabetic mice were significantly reduced (8–10 mice/group). D, E, and F: Measurement of pancreatic β-cell mass and islet size in treated diabetic mice (5 mice/group) and β-cell replication measured as the percentage of BrdU-positive cells (5 mice/group). Data are mean ± SE. Statistical analysis between groups was evaluated by one-way ANOVA, with *P < 0.05 considered significant.