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beta-Cell autophagy in the pathogenesis of type 1 diabetes

机译:β细胞自噬在1型糖尿病发病机制中的应用

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摘要

Type 1 diabetes is an insulin-dependent, autoimmune disease where the pancreatic beta cells are destroyed resulting in hyperglyce-mia. This multifactorial disease involves multiple environmental and genetic factors, and has no clear etiology. Accumulating evidence suggests that early signaling defects within the beta cells may promote a change in the local immune milieu leading to autoimmunity. Therefore, many studies have been focused on intrinsic beta-cell mechanisms that aid in the restoration of cellular homeostasis under environmental conditions that cause dysfunction. One of these intrinsic mechanisms to promote homeostasis is autophagy, defects which are clearly linked with p-cell dysfunction in the context of type 2 diabetes. Recent studies have now also pointed towards beta-cell autophagy defects in the context of type 1 diabetes. In this perspectives review, we will discuss the evidence supporting a role for beta-cell autophagy in the pathogenesis of type 1 diabetes, including a potential role for unconventional secretion of autophagosomes/lysosomes in the changing dialogue between the beta cell and immune cells.
机译:1型糖尿病是一种胰岛素依赖性自身免疫性疾病,胰腺β细胞被破坏,导致高血糖血症。这种多因素疾病涉及多种环境和遗传因素,没有明确的病因。越来越多的证据表明,β细胞内的早期信号缺陷可能会促进局部免疫环境的变化,从而导致自身免疫。因此,许多研究都集中在内在的β细胞机制上,这些机制有助于在导致功能障碍的环境条件下恢复细胞稳态。促进体内平衡的内在机制之一是自噬,在2型糖尿病的背景下,这种缺陷与p细胞功能障碍明显相关。最近的研究现在也指出了 1 型糖尿病背景下的 β 细胞自噬缺陷。在这篇观点综述中,我们将讨论支持β细胞自噬在1型糖尿病发病机制中的作用的证据,包括自噬体/溶酶体非常规分泌在β细胞和免疫细胞之间不断变化的对话中的潜在作用。

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