Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
Department of Medicine, Vanderbilt University Medical Center, 2213 Garland Ave, MRB IV 7465, Nashville, TN, 37232, USA.
Curr Diab Rep. 2019 Aug 9;19(9):81. doi: 10.1007/s11892-019-1196-4.
This review summarizes the alterations in the β-cell observed in type 2 diabetes (T2D), focusing on changes in β-cell identity and mass and changes associated with metabolism and intracellular signaling.
In the setting of T2D, β-cells undergo changes in gene expression, reverting to a more immature state and in some cases transdifferentiating into other islet cell types. Alleviation of metabolic stress, ER stress, and maladaptive prostaglandin signaling could improve β-cell function and survival. The β-cell defects leading to T2D likely differ in different individuals and include variations in β-cell mass, development, β-cell expansion, responses to ER and oxidative stress, insulin production and secretion, and intracellular signaling pathways. The recent recognition that some β-cells undergo dedifferentiation without dying in T2D suggests strategies to revive these cells and rejuvenate their functionality.
本文综述了 2 型糖尿病(T2D)中β细胞的变化,重点关注β细胞特性和数量的变化,以及与代谢和细胞内信号转导相关的变化。
在 T2D 环境下,β细胞发生基因表达的改变,恢复到更不成熟的状态,在某些情况下会转分化为其他胰岛细胞类型。减轻代谢应激、内质网应激和适应性前列腺素信号转导可以改善β细胞的功能和存活。导致 T2D 的β细胞缺陷在不同个体中可能不同,包括β细胞数量、发育、β细胞扩张、对内质网和氧化应激的反应、胰岛素的产生和分泌以及细胞内信号通路的差异。最近的研究发现,一些β细胞在 T2D 中不会死亡而发生去分化,这提示了一些策略,可能可以恢复这些细胞并使它们的功能恢复活力。