Karampelias Christos, Liu Ka-Cheuk, Tengholm Anders, Andersson Olov
Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.
Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Uppsala, Sweden.
Nat Chem Biol. 2025 Jan 29. doi: 10.1038/s41589-024-01822-y.
Diabetes is characterized by variable loss of insulin-producing beta cells, and new regenerative approaches to increasing the functional beta cell mass of patients hold promise for reversing disease progression. In this Review, we summarize recent chemical biology breakthroughs advancing our knowledge of beta cell regeneration. We present current chemical-based tools, sensors and mechanistic insights into pathways that can be targeted to enhance beta cell regeneration in model organisms. We group the pathways according to the cellular processes they affect, that is, proliferation, conversion of other mature cell types to beta cells and beta cell differentiation from progenitor-like populations. We also suggest assays for assessing the functionality of the regenerated beta cells. Although regeneration processes differ between animal models, such as zebrafish, mice and pigs, regenerative mechanisms identified in any one animal model may be translatable to humans. Overall, chemical biology-based approaches in beta cell regeneration give hope that specific molecular pathways can be targeted to enhance beta cell regeneration.
糖尿病的特征是产生胰岛素的β细胞出现不同程度的损失，而增加患者功能性β细胞数量的新再生方法有望逆转疾病进展。在本综述中，我们总结了近期化学生物学的突破，这些突破增进了我们对β细胞再生的了解。我们介绍了当前基于化学的工具、传感器以及对相关途径的机制性见解，这些途径可作为靶点以增强模式生物中的β细胞再生。我们根据这些途径所影响的细胞过程对其进行分类，即增殖、其他成熟细胞类型向β细胞的转化以及祖细胞样群体向β细胞的分化。我们还提出了评估再生β细胞功能的检测方法。尽管斑马鱼、小鼠和猪等动物模型的再生过程有所不同，但在任何一种动物模型中确定的再生机制都可能适用于人类。总体而言，基于化学生物学的β细胞再生方法让人们看到了通过靶向特定分子途径来增强β细胞再生的希望。
