Fig. 4: In vivo real-time monitoring of β-cell proliferation during pregnancy.

A Time courses of luciferase activity in plasma of 3 months old female iβKi67p-Gluc mice on C57BL/6 background during pregnancy relative to those on day 0. Preg (+) indicates mice which had become pregnant, based on subsequent delivery (red). Preg (-) indicates mice which had not been mated. The day when a vaginal plug was identified was defined as day 0 (blue). Solid lines and dotted lines indicate average and individual values, respectively. B The area under the curve of the plasma luciferase activity of Preg (+) mice or Preg (-) mice during the experimental period. C Ki67⁺/Ins⁺ cell ratios in insulin positive cells of 3 months old female iβKi67p-Gluc mice on day 0, 12, and 21 after mating relative to those on day 0; representative images are shown in the right three panels. Each arrowhead denotes a Ki67⁺/Ins⁺ cell. Scale bars denote 50 µm. D Linear relationship between relative luciferase activity and %Ki67⁺/Ins⁺ β-cells. Open circles indicate relative luciferase activity and %Ki67⁺/Ins⁺ cells in individual iβKi67p-Gluc mice after mating relative to those on day 0 (r = 0.812, P = 0.0013).Data are presented as means ± SEM. *p < 0.05, **p < 0.01, assessed by one-way repeated-measures ANOVA followed by Tukey multiple comparison test for the various time points A, two-sided unpaired t-test B, or one-way ANOVA followed by Bonferroni’s post hoc test C. Pearson’s correlation coefficient (two-sided) was used to determine the correlation D. A, B n = 8 independent animals for Preg (+), n = 9 independent animals for Preg (-), from ten independent experiments. C, D n = 4 independent animals for each group, from three independent experiments. Exact P values are A, P = 0.0013 (day 0 vs. day 6), P = 2.0E-4 (day 0 vs. day 9), P = 1.4E-4 (day 0 vs. day 12), P = 0.032 (day 0 vs. day 15); B, P = 0.0087; C P = 9.5E-4 (day 0 vs. day 12), P = 0.010 (day 12 vs. day 21). Source data are provided as a Source Data file.