Fig. 3: In vivo real-time monitoring of β-cell proliferation induced by neuronal signaling.

A Time courses of luciferase activity in plasma from 3 months old male iβKi67p-Gluc mice on C57BL/6 background after L-MEK administration relative to those on day 0 (L-MEK, red). 3 months old male iβKi67p-Gluc mice after LacZ administration served as controls (LacZ, blue). Solid lines and dotted lines indicate average and individual values, respectively. B The area under the curve of the plasma luciferase activity of L-MEK or LacZ during the experimental period. C Ki67 and insulin co-positive cell (Ki67⁺/Ins⁺ cells) ratios in insulin positive cells of 3 months old male iβKi67p-Gluc mice on day 0, 2, and 10 after L-MEK administration 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⁺ β-cells in individual iβKi67p-Gluc mice after L-MEK administration relative to those on day 0 (r = 0.835, P = 0.00073). Data are presented as means ± SEM. **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 = 4 independent samples for L-MEK group, n = 3 independent samples for LacZ group. Results are representative of two independent experiments. C, D n = 4 independent animals for each group, from four independent experiments. Exact P values are A, P = 2.4E-7 (day 0 vs. day 2), P = 0.0046 (day 0 vs. day 3); B P = 0.0018; C P = 1.9E-4 (day 0 vs. day 2), P = 0.0082 (day 2 vs. day 10). Source data are provided as a Source Data file.