Schematic illustrating the consequences of Pax4 ectopic expression in somatostatin-expressing δ cells. Upon Pax4 expression in δ cells (1), these cells are converted into β-like cells (2 and 3). This leads to a disruption of islet homeostasis, mainly because of a local somatostatin shortage, further inducing the mobilization of ductal precursor cells (4), with such precursors reexpressing the proendocrine gene Neurog3 (5). The latter cells undergo EMT before giving rise to insulin⁺, glucagon⁺, and somatostatin⁺ cells in normal/developmental proportions (6), and neogenerated somatostatin⁺ cells are yet again converted into β-like cells. Such a continuous cycle of regeneration and conversion results in insulin⁺ cell hyperplasia, islet hypertrophy, and islet neogenesis (7).