科研之友
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摘要
This review considers the role of alpha-cells in beta-cell generation and regeneration. We present recent evidence obtained from lineage-tracing studies showing that alpha-cells can serve as progenitors of beta-cells and present a hypothetical model how injured beta-cells might activate alpha-cells in adult islets to promote beta-cell regeneration. beta-cells appear to arise by way of their trans-differentiation from undifferentiated a progenitor cells, pro-alpha-cells, both during embryonic development of the islets and in the adult pancreas in response to beta-cell injuries. Plasticity of alpha-cells is endowed by the expression of the gene encoding proglucagon, a prohormone that can give rise to glucagon and glucagon-like peptides (GLPs). The production of glucagon from proglucagon is characteristic of fully-differentiated alpha-cells whereas GLP-1 becomes a product of undifferentiated alpha-cells. GLP-1, a cell growth and survival factor, is proposed to promote the expansion of undifferentiated pro-alpha-cells during development. beta-cells arise from pro-alpha-cells by a change in the relative amounts of the transcription factors Arx and Pax4, master regulators of the alpha- and beta-cell lineages, respectively. A paracrine/autocrine model is proposed whereby injuries of beta-cells in adult islets induce the production and release of factors, such as stromal cell-derived factor-1, that cause the dedifferentiation of adjacent alpha-cells into pro-alpha-cells. Pro-alpha-cells produce GLP-1 and its receptor that renders them competent to trans-differentiate into beta-cells. The trans-differentiation of pro-alpha-cells into beta-cells provides a potentially exploitable mechanism for the regeneration of beta-cells in individuals with type 1 diabetes.
- 出版日期2012-6
