Insulin’s other life: an autoantigen in type 1 diabetes,Immunology and Cell Biology

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Insulin’s other life: an autoantigen in type 1 diabetes
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2021-02-01 , DOI: 10.1111/imcb.12442
Stuart I Mannering _{1,

2} , Pushpak Bhattacharjee ₁

Affiliation

One hundred years ago, Frederick Banting, John Macleod, Charles Best and James Collip, and their collaborators, discovered insulin. This discovery paved the way to saving countless lives and ushered in the “Insulin Era.” Since the discovery of insulin, we have made enormous strides in understanding its role in metabolism and diabetes. Insulin has played a dramatic role in the treatment of people with diabetes; particularly type 1 diabetes (T1D). Insulin replacement is a life‐saving therapy for people with T1D and some with type 2 diabetes. T1D is an autoimmune disease caused by the T‐cell‐mediated destruction of the pancreatic insulin‐producing beta cells that leads to a primary insulin deficiency. It has become increasingly clear that insulin, and its precursors preproinsulin (PPI) and proinsulin (PI), can play another role—not as a hormone but as an autoantigen in T1D. Here we review the role played by the products of the INS gene as autoantigens in people with T1D. From many elegant animal studies, it is clear that T‐cell responses to insulin, PPI and PI are essential for T1D to develop. Here we review the evidence that autoimmune responses to insulin and PPI arise in people with T1D and discuss the recently described neoepitopes derived from the products of the insulin gene. Finally, we look forward to new approaches to deliver epitopes derived from PPI, PI and insulin that may allow immune tolerance to pancreatic beta cells to be restored in people with, or at risk of, T1D.

中文翻译：

胰岛素的另一种生命：1 型糖尿病的自身抗原

一百年前，Frederick Banting、John Macleod、Charles Best 和 James Collip 以及他们的合作者发现了胰岛素。这一发现为挽救无数生命铺平了道路，开启了“胰岛素时代”。自从发现胰岛素以来，我们在理解其在代谢和糖尿病中的作用方面取得了巨大进步。胰岛素在糖尿病患者的治疗中发挥了重要作用。特别是 1 型糖尿病 (T1D)。对于 T1D 患者和部分 2 型糖尿病患者，胰岛素替代治疗是一种挽救生命的疗法。T1D 是一种自身免疫性疾病，由 T 细胞介导的胰腺产生胰岛素的 β 细胞破坏，导致原发性胰岛素缺乏。越来越清楚的是，胰岛素及其前体胰岛素原 (PPI) 和胰岛素原 (PI)，可以发挥另一个作用——不是作为激素，而是作为 T1D 中的自身抗原。下面我们回顾一下这些产品所起的作用INS基因作为 T1D 患者的自身抗原。许多优雅的动物研究表明，T 细胞对胰岛素、PPI 和 PI 的反应对于 T1D 的发展至关重要。在这里，我们回顾了 T1D 患者对胰岛素和 PPI 的自身免疫反应的证据，并讨论了最近描述的源自胰岛素基因产物的新表位。最后，我们期待提供源自 PPI、PI 和胰岛素的表位的新方法，这些方法可能使患有 T1D 或有患 T1D 风险的人恢复对胰腺 β 细胞的免疫耐受性。

更新日期：2021-02-01

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