Transdifferentiation of pancreatic α-cells into insulin-secreting cells: From experimental models to underlying mechanisms

Abstract

Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are currently being investigated to create insulin-producing β cells to replace deficient β cells, including the differentiation of either stem or progenitor cells, and the newly uncovered transdifferentiation of mature non-β islet cell types. However, in order to correctly drive any cell to adopt a new β-cell fate, a better understanding of the in vivo mechanisms involved in the plasticity and biology of islet cells is urgently required. Here, we review the recent studies reporting the phenomenon of transdifferentiation of α cells into β cells by focusing on the major candidates and contexts revealed to be involved in adult β-cell regeneration through this process. The possible underlying mechanisms of transdifferentiation and the interactions between several key factors involved in the process are also addressed. We propose that it is of importance to further study the molecular and cellular mechanisms underlying α- to β-cell transdifferentiation, in order to make β-cell regeneration from α cells a relevant and realizable strategy for developing cell-replacement therapy.

Keywords: α-cell; β-cell; Transdifferentiation; Diabetes mellitus; Cell-replacement therapy

Core tip: Recent works highlighted the phenomenon of transdifferentiation of pancreatic α cells into β cells, which has drawn much attention in the field. Considering that α-cell transdifferentiation could be used as a new strategy of cell replacement therapy for the treatment of diabetes, because of the presence of α cells in the pancreas of both type 1 and 2 diabetics, we believe that it is relevant to elucidate the cellular and molecular events in α- to β-cell conversion. Our review focuses on the recent experimental α-cell transdifferentiation models, highlighting the insight provided by these works into the candidates and contexts revealed to be involved in this process.