Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, MA, USA.
Islets. 2012 May-Jun;4(3):188-98. doi: 10.4161/isl.20500.
This review considers the role of α-cells in β-cell generation and regeneration. We present recent evidence obtained from lineage-tracing studies showing that α-cells can serve as progenitors of β-cells and present a hypothetical model how injured β-cells might activate α-cells in adult islets to promote β-cell regeneration. β-cells appear to arise by way of their trans-differentiation from undifferentiated α progenitor cells, pro-α-cells, both during embryonic development of the islets and in the adult pancreas in response to β-cell injuries. Plasticity of α-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 α-cells whereas GLP-1 is a product of undifferentiated α-cells. GLP-1, a cell growth and survival factor, is proposed to promote the expansion of neurogenin3-expressing, undifferentiated pro-α-cells during development. β-cells arise from pro-α-cells by a change in the relative amounts of the transcription factors Arx and Pax4, master regulators of the α- and β-cell lineages, respectively. A paracrine/autocrine model is proposed whereby injuries of β-cells in adult islets induce the production and release of factors, such as stromal cell-derived factor-1, that cause the de-differentiation of adjacent α-cells into pro-α-cells. Pro-α-cells produce GLP-1 and its receptor that renders them competent to trans-differentiate into β-cells. The trans-differentiation of pro-α-cells into β-cells provides a potentially exploitable mechanism for the regeneration of β-cells in individuals with type 1 diabetes.
这篇综述探讨了α细胞在β细胞生成和再生中的作用。我们呈现了最近的研究证据，这些证据来自谱系追踪研究，表明α细胞可以作为β细胞的祖细胞，并提出了一个假设模型，即受损的β细胞如何激活成年胰岛中的α细胞以促进β细胞再生。β细胞似乎是通过其从未分化的α祖细胞，即前α细胞，在胰岛的胚胎发育过程中和成年胰腺中β细胞损伤时的转分化而产生的。α细胞的可塑性是由编码前胰高血糖素的基因表达赋予的，前胰高血糖素是一种可以产生胰高血糖素和胰高血糖素样肽（GLP）的前激素。前胰高血糖素产生胰高血糖素是完全分化的α细胞的特征，而 GLP-1 是未分化的α细胞的产物。GLP-1 是一种细胞生长和存活因子，据推测它可以促进神经基因 3 表达的未分化前α细胞在发育过程中的扩张。β细胞从前α细胞产生是通过转录因子 Arx 和 Pax4 的相对数量的变化，分别是α和β细胞谱系的主要调节因子。提出了一个旁分泌/自分泌模型，即成年胰岛中的β细胞损伤诱导产生和释放因子，如基质细胞衍生因子-1，导致相邻的α细胞去分化为前α细胞。前α细胞产生 GLP-1 和其受体，使它们有能力转分化为β细胞。前α细胞向β细胞的转分化为 1 型糖尿病患者的β细胞再生提供了一种潜在可利用的机制。
