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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.