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β细胞疗法预防 1 型糖尿病:从基础到临床。

Beta Cell Therapies for Preventing Type 1 Diabetes: From Bench to Bedside.

机构信息

Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.

Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada.

出版信息

Biomolecules. 2020 Dec 16;10(12):1681. doi: 10.3390/biom10121681.

Abstract

Type 1 diabetes (T1D) is a chronic metabolic disease characterized by insulin deficiency, generally resulting from progressive autoimmune-mediated destruction of pancreatic beta cells. While the phenomenon of beta cell autoimmunity continues to be an active area of investigation, recent evidence suggests that beta cell stress responses are also important contributors to disease onset. Here we review the pathways driving different kinds of beta cell dysfunction and their respective therapeutic targets in the prevention of T1D. We discuss opportunities and important open questions around the effectiveness of beta cell therapies and challenges for clinical utility. We further evaluate ways in which beta cell drug therapy could be combined with immunotherapy for preventing T1D in light of our growing appreciation of disease heterogeneity and patient endotypes. Ultimately, the emergence of pharmacologic beta cell therapies for T1D have armed us with new tools and closing the knowledge gaps in T1D etiology will be essential for maximizing the potential of these approaches.

摘要

1 型糖尿病(T1D)是一种慢性代谢性疾病,其特征是胰岛素缺乏,通常是由于胰腺β细胞进行性自身免疫介导的破坏所致。虽然β细胞自身免疫现象仍然是一个活跃的研究领域,但最近的证据表明,β细胞应激反应也是疾病发生的重要因素。在这里,我们回顾了导致不同类型β细胞功能障碍的途径及其各自在预防 T1D 中的治疗靶点。我们讨论了β细胞治疗的有效性方面的机会和重要的开放性问题,以及临床应用的挑战。鉴于我们对疾病异质性和患者内表型的认识不断提高,我们进一步评估了β细胞药物治疗与免疫治疗相结合预防 T1D 的方法。最终,用于 T1D 的药理β细胞治疗方法的出现为我们提供了新的工具,而填补 T1D 病因学中的知识空白对于最大限度地发挥这些方法的潜力至关重要。

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