Ectopic expression of Pax4 in pancreatic δ cells results in β-like cell neogenesis

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