Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, D-85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), D-85764 Neuherberg, Germany.
Int J Mol Sci. 2019 Oct 30;20(21):5417. doi: 10.3390/ijms20215417.
The exponential increase of patients with diabetes mellitus urges for novel therapeutic strategies to reduce the socioeconomic burden of this disease. The loss or dysfunction of insulin-producing β-cells, in patients with type 1 and type 2 diabetes respectively, put these cells at the center of the disease initiation and progression. Therefore, major efforts have been taken to restore the β-cell mass by cell-replacement or regeneration approaches. Implementing novel therapies requires deciphering the developmental mechanisms that generate β-cells and determine the acquisition of their physiological phenotype. In this review, we summarize the current understanding of the mechanisms that coordinate the postnatal maturation of β-cells and define their functional identity. Furthermore, we discuss different routes by which β-cells lose their features and functionality in type 1 and 2 diabetic conditions. We then focus on potential mechanisms to restore the functionality of those β-cell populations that have lost their functional phenotype. Finally, we discuss the recent progress and remaining challenges facing the generation of functional mature β-cells from stem cells for cell-replacement therapy for diabetes treatment.
糖尿病患者的数量呈指数级增长，这促使我们寻求新的治疗策略来减轻这种疾病的社会经济负担。1 型和 2 型糖尿病患者的胰岛素分泌β细胞的缺失或功能障碍，使这些细胞成为疾病发生和进展的核心。因此，人们做出了巨大努力，通过细胞替代或再生方法来恢复β细胞的数量。实施新的治疗方法需要阐明产生β细胞并决定其获得生理表型的发育机制。在这篇综述中，我们总结了目前对协调β细胞出生后成熟的机制以及定义其功能特征的理解。此外，我们还讨论了 1 型和 2 型糖尿病中β细胞丧失特征和功能的不同途径。然后，我们将重点讨论恢复那些丧失功能表型的β细胞群体功能的潜在机制。最后，我们讨论了从干细胞生成功能性成熟β细胞用于细胞替代治疗糖尿病的最新进展和仍然面临的挑战。
