ß1-integrin is a crucial regulator of the exocytotic machinery in pancreatic beta-cells, affecting insulin secretion and integrin trafficking.

α1-整合素是胰腺β细胞胞吐机制的重要调节因子，影响胰岛素分泌和整合素运输。

• 批准号: RGPIN-2017-04658
• 负责人: Wang, Rennian
• 金额: $ 2.48万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711099
• 关键词: integrin; crucial; regulator; exocytotic; machinery

The discovery of insulin in 1921 by Banting and Best laid the foundation for the modern management of diabetes mellitus, a disease that affects millions of Canadians and costs our healthcare system more than $17 billion annually. However, insulin treatment cannot cure diabetes and will not prevent the secondary complications, which are responsible for the devastating morbidity and mortality of this disease. Replacement of insulin-producing (beta) cells through a cell-based therapy (e.g. pancreatic islet transplantation or a bioartificial endocrine pancreas) has the best chance to prevent, reverse or stabilize these complications. However, the scarcity of islets and limitations in our knowledge of the factors influencing islet biology present a major obstacle to the adoption of cell-based therapies as a routine treatment. Advancement in this field requires a thorough understanding of the factors that regulate growth of the islet beta cells and maintain their viability and function. Our previous in vivo and in vitro studies have determined that the interactions of a beta cell receptor, 1-integrin, with extracellular matrix (ECM) proteins are essential for maintaining beta cell function and preventing cell death. Recently we discovered that the loss of 1 integrin in beta cells led to abnormalities in the insulin secretory pathway, including changes in the expression of specific secretory pathway proteins. In addition, alternative members of the integrin receptor family were expressed. As a result, our new research objectives are twofold: (1) to investigate how 1-ECM interactions regulate the expression of secretory pathway proteins in beta cells; and (2) to determine how 1-ECM interactions and the secretory pathway proteins influence which integrins are expressed in beta cells. We believe that these studies will facilitate the development of appropriate tissue engineering strategies for a bioartificial endocrine pancreas. Such a treatment would have far-reaching economic and social benefits.

1921年通过banting和最佳糖尿病管理基础发现了胰岛素，这种疾病影响了数百万加拿大人，每年损失超过170亿美元的医疗保健系统。但是，胰岛素治疗无法治愈糖尿病，并且不会阻止次要并发症，这些并发症是导致该疾病毁灭性发病率和死亡率的原因。通过基于细胞的疗法（例如胰岛移植或生物人工内分泌胰腺）取代产生胰岛素的细胞（β）细胞，这是预防，逆转或稳定这些并发症的最佳机会。但是，我们对影响胰岛生物学因素的知识的胰岛缺乏和局限性是采用基于细胞的疗法作为常规治疗的主要障碍。该领域的进步需要对调节胰岛β细胞生长的因素有透彻的了解并保持其生存力和功能。 我们以前的体内和体外研究已经确定，β细胞受体1-整合素与细胞外基质（ECM）蛋白的相互作用对于维持β细胞功能和预防细胞死亡至关重要。最近，我们发现β细胞中1个整联蛋白的损失导致胰岛素分泌途径异常，包括特定分泌途径蛋白的表达变化。此外，表达了整联蛋白受体家族的替代成员。结果，我们的新研究目标是双重的：（1）研究1-ECM相互作用如何调节β细胞中分泌途径蛋白的表达； （2）确定1-ECM相互作用和分泌途径蛋白如何影响整联蛋白在β细胞中表达。 我们认为，这些研究将促进生物人工内分泌胰腺的适当组织工程策略的发展。这种治疗将具有深远的经济和社会利益。