Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Peptides. 2018 Feb;100:85-93. doi: 10.1016/j.peptides.2017.12.002.
Autophagy is a highly conserved intracellular recycling pathway that serves to recycle damaged organelles/proteins or superfluous nutrients during times of nutritional stress to provide energy to maintain intracellular homeostasis and sustain core metabolic functions. Under these conditions, autophagy functions as a cell survival mechanism but impairment of this pathway can lead to pro-death stimuli. Due to their role in synthesising and secreting insulin, pancreatic β-cells have a high requirement for robust degradation pathways. Recent research suggests that functional autophagy is required to maintain β-cell survival and function in response to high fat diet suggesting a pro-survival role. However, a role for autophagy has also been implicated in the pathogenesis of type 2 diabetes. Thus, the pro-survival vs pro-death role of autophagy in regulating β-cell mass requires discussion. Emerging evidence suggests that Glucagon-Like Peptide-1 (GLP-1) may exert beneficial effects on glucose homeostasis via autophagy-dependent pathways both in pancreatic β-cells and in other cell types. The aim of the current review is to: i) summarise the literature surrounding β-cell autophagy and its pro-death vs pro-survival role in regulating β-cell mass; ii) review the literature describing the impact of GLP-1 on β-cell autophagy and in other cell types; iii) discuss the potential underlying mechanisms.
自噬是一种高度保守的细胞内回收途径，它在营养压力时期回收受损的细胞器/蛋白质或多余的营养物质，为维持细胞内稳态和维持核心代谢功能提供能量。在这些条件下，自噬作为一种细胞存活机制发挥作用，但该途径的损伤会导致促死亡刺激。由于它们在合成和分泌胰岛素中的作用，胰腺β细胞对强大的降解途径有很高的要求。最近的研究表明，功能正常的自噬对于高脂饮食下β细胞的存活和功能至关重要，表明其具有促生存作用。然而，自噬在 2 型糖尿病的发病机制中也有作用。因此，自噬在调节β细胞质量方面的促生存作用与促死亡作用需要讨论。新出现的证据表明，胰高血糖素样肽-1（GLP-1）可能通过自噬依赖途径在胰腺β细胞和其他细胞类型中对葡萄糖稳态发挥有益作用。本综述的目的是：i）总结围绕β细胞自噬及其在调节β细胞质量方面的促死亡作用与促生存作用的文献；ii）综述描述 GLP-1 对β细胞自噬和其他细胞类型的影响的文献；iii）讨论潜在的潜在机制。
