β cell neogenesis from ducts and phenotypic conversion of residual islet cells in the adult pancreas of glucose intolerant mice induced by selective alloxan perfusion

Abstract

The aim of this study was to clarify the pattern of β cell neogenesis in the alloxan-perfused, β cells-depleted segment of glucose intolerant mice induced by selective alloxan perfusion. First, duct cells proliferated in the perfused segment, then cells co-expressing multiple islet hormones and transcription factors such as PDX-1, Nkx2.2, Isl1, and Pax6 were observed in duct cells, and newly formed islet-like cell clusters (ICCs) containing β cells were recognized. In residual β cell-depleted islets, glucagon or somatostatin and PDX-1 double-positive immature endocrine cells were recognized. Glucagon or somatostatin, insulin and PDX-1 triple-positive cells then appeared and these cells appeared to undergo terminal differentiation into β cells. In conclusion, we demonstrated at least two different processes of β cell neogenesis, i.e., formation of new ICCs from ductal epithelium and redifferentiation of residual non-β islet cells in this model. In addition, transcription factors that appear in the processes of endocrine cell development may also play essential roles during β cell neogenesis from duct cells.