Investigating the role of Viperin in beta cell survival and the development of type 1 diabetes.

糖尿病目前影响全球4.63亿人，其中约10%患有1型糖尿病（T1D），这是儿童最常见的糖尿病形式。在T1D期间，胰腺中产生胰岛素的细胞（β细胞）受到免疫系统的攻击，原因我们还不完全了解，导致胰岛素丢失，血糖水平升高和许多并发症。确定防止β细胞损失的新方法对于开发这种疾病的新疗法至关重要。同样，迫切需要改善胰岛移植（一些T1D患者接受）功能和存活的新方法来改善血糖控制。我们已经确定了一种名为Viperin的蛋白质，它是人体免疫系统的一部分，在体外（实验室中的一个培养皿中）暴露于免疫攻击过程中释放的物质后，在控制β细胞存活方面发挥着作用。在本申请中，我们将通过遗传改变T1D小鼠模型和小鼠胰岛移植物中的Viperin水平来扩展这些发现，以确定Viperin是否在β细胞存活、炎症和功能中起作用。我们还将探索Viperin控制细胞存活的机制，并将我们的工作扩展到人体组织。未来的研究方向包括探索Viperin在β细胞对系统性病毒感染的反应中的作用，筛选Viperin的激活剂（作为候选药物），以及研究Viperin在其他与T1D相关的细胞类型中的作用。如果该项目验证了Viperin在β细胞中的保护作用，这将可能导致开发新的治疗方法来治疗T1D，并改善临床胰岛移植。

Diabetes currently affects 463 million people worldwide, of which approximately 10% suffer from type 1 diabetes (T1D), the most common form of diabetes in children. During T1D the cells in the pancreas that produce insulin (beta cells) are attacked by the immune system, for reasons we don't yet fully understand, leading to a loss of insulin and increased blood sugar levels and a number of complications. Identifying new ways to prevent the loss of beta cells is vital to develop new treatments for this disease. Likewise, new ways to improve the function and survival of islet transplants (which some T1D patients receive) are urgently needed to improve control of blood sugar. We have identified that a protein called Viperin, that forms part of the body's immune system, plays a role in controlling beta cell survival following exposure to substances released during immune attack, in vitro (in a dish in the lab). In the present application, we will extend these findings by genetically altering Viperin levels in mouse models of T1D and in mouse islet transplants, to determine if Viperin plays a role in beta cell survival, inflammation and function. We will also explore the mechanisms by which Viperin controls cell survival, and extend our work to human tissue. Future directions include exploring the role of Viperin in the response of beta cells to systemic viral infection, screening for activators of Viperin (as drug candidates) and investigating Viperin action in other cell types relevant to T1D. If this project validates a protective role for Viperin in beta cells, this will potentially lead to the development of new therapeutic approaches for the treatment of T1D in people, and improvement of clinical islet transplantation.