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Adult Pancreatic Alpha-Cells: A New Source of Cells for Beta-Cell Regeneration

机译:成人胰腺α细胞:β细胞再生的新细胞来源。

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Beta-cell deficit is the major pathological feature in type 1 and type 2 diabetes patients, and plays a key role in disease progression. In principle, beta-cell regeneration can occur by replication of pre-existing beta-cells, or by beta-cell neogenesis from stem/progenitors. Unfortunately, beta-cell replication is limited by the almost complete absence of beta-cells in patients with type 1 diabetes, and the increasing recognition that the beta-cell replicative capacity declines severely with age. Therefore, beta-cell neogenesis has received increasing interest. Many different cell types within the pancreas have been suggested as potential beta-cell stem/progenitor cells, but the data have been conflicting. In some cases, this may be due to different regeneration models. On the other hand, different results have been obtained with similar regeneration models, leading to confusion about the nature and existence of beta-cell neogenesis in adult animals. Here, we review the major candidates for adult regeneration pathways, and focus on the recent discovery that alpha-cells can function as a novel beta-cell progenitor. Of note, this is a pathway that appears to be unique to beta-cell neogenesis in the adult, as the embryonic pathway of beta-cell neogenesis does not proceed through a glucagon-positive intermediate. We conclude that beta-cell neogenesis from alpha-cells is a new pathway of potential therapeutic significance, making it of high importance to elucidate the molecular events in alpha- to beta-cell conversion.
机译:β细胞缺陷是1型和2型糖尿病患者的主要病理特征,并且在疾病进展中起关键作用。原则上,β细胞再生可通过复制先前存在的β细胞或通过干细胞/祖细胞的β细胞新生来进行。不幸的是,β细胞的复制受到1型糖尿病患者几乎完全不存在β细胞的限制,并且人们日益认识到β细胞复制能力会随着年龄的增长而严重下降。因此,β细胞新生已引起越来越多的兴趣。胰腺内有许多不同的细胞类型被认为是潜在的β细胞干/祖细胞,但数据一直存在矛盾。在某些情况下,这可能是由于不同的再生模型。另一方面,在类似的再生模型中已经获得了不同的结果,导致对成年动物中β细胞新生的性质和存在的困惑。在这里,我们审查成人再生途径的主要候选人,并集中在最近的发现,α细胞可以作为一种新型的β细胞祖细胞。值得注意的是,这是成年人中β细胞新生的独特途径,因为β细胞新生的胚胎途径并不通过胰高血糖素阳性中间体来进行。我们得出的结论是,来自α细胞的β细胞新生是具有潜在治疗意义的新途径,因此阐明在α细胞向β细胞转化中的分子事件非常重要。

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