Figure 8.

The ectopic expression of Pax4 in δ cells can induce functional β-like cell neogenesis upon chemically induced β cell ablation. 2.5-mo-old mice were treated with STZ and sacrificed at different time points (A). Immunofluorescence assessment of insulin-expressing cells in control (B–D) or transgenic (E–G) islets outline a progressive recovery of the β cell mass. Monitoring of the glycemia revealed an expected peak in glycemic levels in both control and transgenic mice (H). However, 2.5 mo after β cell ablation, Sst-Cre::Pax4-OE mice displayed lowered glycemic levels, whereas control animals remained hyperglycemic (many of these mice died during the course of the monitoring). Quantitative analyses indicated an approximate doubling in the β cell area in transgenic islets 3 mo after STZ administration (I). Lineage tracing experiments of somatostatin-expressing cells performed on pancreas sections of STZ-treated mice showing β-gal⁺/insulin⁺ cells in transgenic islets (J and K, arrows). For the purpose of clarity, in selected photographs, islets are outlined with dashed white lines. All values are depicted as mean ± SEM of n = 6 and n = 4 independent control and transgenic animals, respectively. Statistical analyses were performed using the Mann–Whitney test and multiple t tests (****, P < 0.0001; *, P < 0.05). Bars: 50 µm; (insets) 20 µm. INS, insulin.