Role of Pax4/Pax6 in pancreatic β-cell differentiation and maintaining its function

众所周知，Pax4在胰腺发育中起着重要作用。在我们的研究中，我们发现Pax4过表达诱导前体细胞向胰岛素生成细胞分化。Pax4过表达还能诱导包括GLUT2在内的多种β细胞特异性因子，表明Pax4促进了p细胞的分化。此外，我们发现Pax4具有转录阻遏因子的功能，并发现了几个与Pax4结合的候选分子，可以作为Pax4的协同阻遏因子。此外，我们发现Pax6在维持β细胞功能中起着重要作用；我们发现，在Pax6（+/-）小鼠中，葡萄糖刺激的胰岛素分泌受损，尽管胰腺形态和胰岛素含量没有差异。这些结果表明Pax6在葡萄糖刺激胰岛素分泌中起重要作用。

Pax4 is well known to play some important role in pancreas development. In our study, we showed that Pax4 overexpression induces differentiation from precursor cells to insulin-producing cells. Various β-cell-specific factors including GLUT2 were also induced by Pax4 overexpression, indicating that Pax4 facilitates p-cell differentiation. In addition, we showed that Pax4 functions as a transcriptional repressor and found several candidate molecules which binds to Pax4 and could function as a co-repressor of Pax4.Also, we found that Pax6 plays some important role in maintaining β-cell function; we showed that in Pax6 (+/-) mice glucose-stimulated insulin secretion was impaired, although there was no difference in pancreas morphology and insulin content. These results indicate that Pax6 plays some important role in glucose-stimulated insulin secretion.