Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
Nat Rev Endocrinol. 2018 Dec;14(12):694-704. doi: 10.1038/s41574-018-0097-y.
Findings from the past 10 years have placed the glucagon-secreting pancreatic α-cell centre stage in the development of diabetes mellitus, a disease affecting almost one in every ten adults worldwide. Glucagon secretion is reduced in patients with type 1 diabetes mellitus, increasing the risk of insulin-induced hypoglycaemia, but is enhanced in type 2 diabetes mellitus, exacerbating the effects of diminished insulin release and action on blood levels of glucose. A better understanding of the mechanisms underlying these changes is therefore an important goal. RNA sequencing reveals that, despite their opposing roles in the control of blood levels of glucose, α-cells and β-cells have remarkably similar patterns of gene expression. This similarity might explain the fairly facile interconversion between these cells and the ability of the α-cell compartment to serve as a source of new β-cells in models of extreme β-cell loss that mimic type 1 diabetes mellitus. Emerging data suggest that GABA might facilitate this interconversion, whereas the amino acid glutamine serves as a liver-derived factor to promote α-cell replication and maintenance of α-cell mass. Here, we survey these developments and their therapeutic implications for patients with diabetes mellitus.
过去十年的研究结果表明，在全球近十分之一的成年人都受到影响的糖尿病的发生发展中，胰高血糖素分泌的胰岛α细胞处于中心地位。1 型糖尿病患者的胰高血糖素分泌减少，增加了胰岛素诱导低血糖的风险，但在 2 型糖尿病中却增强了，加剧了胰岛素释放和作用对血糖水平的影响。因此，更好地了解这些变化背后的机制是一个重要的目标。RNA 测序表明，尽管α细胞和β细胞在控制血糖水平方面发挥着相反的作用，但它们的基因表达模式却惊人地相似。这种相似性可能解释了这些细胞之间相当容易的相互转化，以及α细胞区室在模拟 1 型糖尿病的极端β细胞丢失的模型中作为新β细胞来源的能力。新出现的数据表明，GABA 可能促进这种相互转化，而氨基酸谷氨酰胺则作为一种肝脏来源的因子，促进α细胞的复制和α细胞质量的维持。在这里，我们调查了这些进展及其对糖尿病患者的治疗意义。
