Chung Cheng-Ho, Levine Fred
Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute 10901 N. Torrey Pines Road, CA 92037, USA.
Rev Diabet Stud. 2010 Summer;7(2):124-31. doi: 10.1900/RDS.2010.7.124. Epub 2010 Aug 10.
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.
β细胞缺陷是1型和2型糖尿病患者的主要病理特征，在疾病进展中起关键作用。原则上，β细胞再生可通过已存在的β细胞复制，或由干细胞/祖细胞生成新的β细胞来实现。不幸的是，1型糖尿病患者几乎完全缺乏β细胞，限制了β细胞的复制，而且人们越来越认识到β细胞的复制能力会随着年龄的增长而严重下降。因此，β细胞新生受到了越来越多的关注。胰腺内许多不同类型的细胞被认为是潜在的β细胞干细胞/祖细胞，但相关数据相互矛盾。在某些情况下，这可能是由于不同的再生模型。另一方面，使用相似的再生模型却得到了不同的结果，这导致人们对成年动物中β细胞新生的本质和存在产生困惑。在此，我们综述成年再生途径的主要候选者，并着重介绍最近的一项发现，即α细胞可作为一种新的β细胞祖细胞发挥作用。值得注意的是，这是一条在成年期β细胞新生中似乎独有的途径，因为β细胞胚胎期新生途径并不经过胰高血糖素阳性中间体。我们得出结论，α细胞生成β细胞是一条具有潜在治疗意义的新途径，因此阐明α细胞向β细胞转化过程中的分子事件至关重要。
