Program in Gene Function, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Curr Opin Endocrinol Diabetes Obes. 2010 Apr;17(2):107-12. doi: 10.1097/MED.0b013e3283372843.
beta-Cell death is an important pathogenic component of both type 1 and type 2 diabetes. However, the specific molecular pathways and interactions involved in this process are not completely understood. Increasing evidence indicates that a type of cell stress called endoplasmic reticulum stress (ER stress) plays an important role in beta-cell death. In the present article, we discuss a potential paradigm of ER stress-mediated beta-cell death.
Upon ER stress conditions, a signaling network termed the unfolded protein response (UPR) is activated. The UPR regulates adaptive effectors to attenuate ER stress and restore ER homeostasis promoting cell survival. Paradoxically the UPR also regulates apoptotic effectors. When adaptive effectors fail to attenuate ER stress, these apoptotic effectors take into effect leading to cell death. The nature of this switch between life and death is currently under study.
Depending on the nature of the stress condition, the UPR either protects beta cells or promotes their death. The mechanisms of this switch are not well understood but involve the balance between adaptive and apoptotic factors regulated by the UPR. In the present article, we review examples of this UPR balancing act between life and death and the potential mechanisms involved.
β细胞死亡是 1 型和 2 型糖尿病的重要发病机制之一。然而，这一过程中涉及的具体分子途径和相互作用尚不完全清楚。越来越多的证据表明，一种称为内质网应激（ER 应激）的细胞应激在β细胞死亡中起重要作用。在本文中，我们讨论了 ER 应激介导的β细胞死亡的潜在范例。
在 ER 应激条件下，一种称为未折叠蛋白反应（UPR）的信号网络被激活。UPR 调节适应性效应物以减轻 ER 应激并恢复 ER 稳态，促进细胞存活。矛盾的是，UPR 还调节凋亡效应物。当适应性效应物未能减轻 ER 应激时，这些凋亡效应物开始起作用导致细胞死亡。这种生与死之间的转换的性质目前正在研究中。
根据应激条件的性质，UPR 要么保护β细胞，要么促进其死亡。这种转换的机制尚不清楚，但涉及由 UPR 调节的适应性和凋亡因子之间的平衡。在本文中，我们回顾了 UPR 在生与死之间的这种平衡行为的例子及其潜在的机制。
