Ectopic expression of <i>Pax4</i> in pancreatic δ cells results in β-like cell neogenesis

Abstract

The recent demonstration that pancreatic α cells can be continuously regenerated and converted into β-like cells upon ectopic expression of <i>Pax4</i> opened new avenues of research in the endocrine cell differentiation and diabetes fields. To determine whether such plasticity was also shared by δ cells, we generated and characterized transgenic animals that express <i>Pax4</i> specifically in somatostatin-expressing cells. We demonstrate that the ectopic expression of <i>Pax4</i> in δ cells is sufficient to induce their conversion into functional β-like cells. Importantly, this conversion induces compensatory mechanisms involving the reactivation of endocrine developmental processes that result in dramatic β-like cell hyperplasia. Importantly, these β-like cells are functional and can partly reverse the consequences of chemically induced diabetes.