Hao Meihua, Sebag Sara C, Qian Qingwen, Yang Ling
Department of Anatomy and Cell Biology, Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
eGastroenterology. 2024 Oct;2(3). doi: 10.1136/egastro-2024-100096. Epub 2024 Aug 29.
Endocrine and exocrine functions of the pancreas control nutritional absorption, utilisation and systemic metabolic homeostasis. Under basal conditions, the lysosome is pivotal in regulating intracellular organelles and metabolite turnover. In response to acute or chronic stress, the lysosome senses metabolic flux and inflammatory challenges, thereby initiating the adaptive programme to re-establish cellular homeostasis. A growing body of evidence has demonstrated the pathophysiological relevance of the lysosomal stress response in metabolic diseases in diverse sets of tissues/organs, such as the liver and the heart. In this review, we discuss the pathological relevance of pancreatic lysosome stress in diabetes mellitus. We begin by summarising lysosomal biology, followed by exploring the immune and metabolic functions of lysosomes and finally discussing the interplay between lysosomal stress and the pathogenesis of pancreatic diseases. Ultimately, our review aims to enhance our understanding of lysosomal stress in disease pathogenesis, which could potentially lead to the discovery of innovative treatment methods for these conditions.
胰腺的内分泌和外分泌功能控制营养物质的吸收、利用以及全身代谢稳态。在基础条件下，溶酶体在调节细胞内细胞器和代谢物周转方面起着关键作用。响应急性或慢性应激时，溶酶体感知代谢通量和炎症挑战，从而启动适应性程序以重新建立细胞稳态。越来越多的证据表明溶酶体应激反应在肝脏和心脏等不同组织/器官的代谢性疾病中的病理生理相关性。在本综述中，我们讨论胰腺溶酶体应激在糖尿病中的病理相关性。我们首先总结溶酶体生物学，接着探讨溶酶体的免疫和代谢功能，最后讨论溶酶体应激与胰腺疾病发病机制之间的相互作用。最终，我们的综述旨在增进我们对疾病发病机制中溶酶体应激的理解，这可能会促使发现针对这些病症的创新治疗方法。
