(A) Both juvenile and adult islets express a similar level of GLP1R mRNA measured by qPCR (juvenile: n = 6, 0.5–9 years old; adult: n = 6, 20–60 years old). (B) Experimental design. After a 2-week islet engraftment period, PBS or Ex-4 was delivered by osmotic pump. The grafts were removed and analyses were performed after 4 weeks of treatment. (C–E) Mouse random glucose (C) and human insulin (D and E) in mice with transplanted juvenile (D, n = 3 donors) or adult (E, n = 3 donors) human islets 48 hours after the implantation of pumps with PBS or Ex-4 (n = 13–14 samples). (F) Representative images of juvenile grafts labeled with insulin (green), Ki67 (red), and DAPI (blue). Insets show proliferating Ki67+ cells. Scale bar: 35 μm. (G and H) Percentage of β cell proliferation in grafts from individual juvenile and adult donors (n = 4–8 grafts per donor). Insets are average percentage in each age group. (I) Statistical analysis of data sets in G and H. Error bars represent SEM. *P < 0.05; **P < 0.01; ***P < 0.001. Unpaired 2-tailed Student’s t test or 1-way ANOVA followed by Newman-Keuls multiple-comparisons test (I) was used for statistical analysis. See also Supplemental Figures 2 and 3.