Review: Pancreaticβ-Cell Neogenesis Revisited

Abstract

β-cell neogenesis triggers the generation of newβ-cells from precursor cells. Neogenesis from duct epithelium is the most currently described and the best documented process of differentiation of precursor cells intoβ-cells. It is contributes not only toβ-cell mass expansion during fetal and nonatal life but it is also involved in the maintenance of theβ-cell mass in adults. It is also required for the increase inβ-cell mass in situations of increase insulin demand (obesity, pregnancy). A large number of factors controlling the differentiation ofβ-cells has been identified. They are classified into the following main categories: growth factors, cytokine and inflamatory factors, and hormones such as PTHrP and GLP-1. The fact that intestinal incretin hormone GLP-1 exerts a major trophic role on pancreaticβ-cells provides insights into the possibility to pharmacologically stimulateβ-cell neogenesis. This could have important implications for the of treatment of type 1 and type 2 diabetes. Transdifferentiation, that is, the differentiation of already differentiated cells intoβ-cells, remains controversial.However, more and more studies support this concept. The cells, which can potentially “transdifferentiate” intoβ-cells, can belong to the pancreas (acinar cells) and even islets, or originate from extra-pancreatic tissues such as the liver. Neogenesis from intra-islet precursors also have been proposed and subpopulations of cell precursors inside islets have been described by some authors. Nestin positive cells, which have been considered as the main candidates, appear rather as progenitors of endothelial cells rather thanβ-cells and contribute to angiogenesis rather than neogenesis. To take advantage of the different differentiation processes may be a direction for future cellular therapies. Ultimately, a better understanding of the molecular mechanisms involved inβ-cell neogenesis will allow us to use any type of differentiated and/or undifferentiated cells as a source of potential cell precursors.