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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=668120
• 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, β1-integrin, with extracellular matrix (ECM) proteins are essential for maintaining beta cell function and preventing cell death. Recently we discovered that the loss of β1 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 β1-ECM interactions regulate the expression of secretory pathway proteins in beta cells; and (2) to determine how β1-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，Banting和Best发现了胰岛素，为糖尿病的现代管理奠定了基础，糖尿病是一种影响数百万加拿大人的疾病，每年花费我们的医疗保健系统超过170亿美元。然而，胰岛素治疗不能治愈糖尿病，也不能预防继发性并发症，而继发性并发症是导致糖尿病毁灭性发病率和死亡率的原因。通过基于细胞的治疗（例如胰岛移植或生物人工内分泌胰腺）替代胰岛素产生（β）细胞具有预防、逆转或稳定这些并发症的最佳机会。然而，胰岛的稀缺性和我们对影响胰岛生物学的因素的认识的局限性，是采用基于细胞的疗法作为常规治疗的主要障碍。在这一领域的进步需要彻底了解的因素，调节胰岛β细胞的生长和维持其活力和功能。** 我们之前的体内和体外研究已经确定β细胞受体β1-整联蛋白与细胞外基质（ECM）蛋白的相互作用对于维持β细胞功能和防止细胞死亡至关重要。最近我们发现β细胞中β1整合素的缺失导致胰岛素分泌途径的异常，包括特定分泌途径蛋白表达的改变。此外，表达了整合素受体家族的替代成员。因此，我们的新研究目标是双重的：（1）研究β1-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β1-ECM相互作用和分泌途径蛋白如何影响β细胞中表达的整合素。** 我们相信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。这样的待遇将产生深远的经济和社会效益。**