Beta-Cell Mass And Function In Implants and Pancreas

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DESCRIPTION (provided by applicant): Beta-cells of the islets of Langerhans play important roles in regulating metabolism through the action of secreting insulin. In type 1diabetes, beta cells are quickly damaged or destroyed. In type 2 diabetes, beta-cells appear to be gradually injured over a prolonged period. However, the details of this injury process are poorly understood, in part because we have no method to localize beta-cells in vivo. Attempts to treat diabetes by introducing beta-cells are also limited in part by uncertainty about the fate of the cells. This proposed technology development project is designed to demonstrate new methods of imaging beta-cellls in vivo. We have synthesized novel magnetic resonance imaging (MRI) contrast agents that can diffuse inside cells and accumulate to high concentrations. Preliminary studies suggested that labeled beta-cells grew and secreted insulin normally in response to glucose. We plan to implant these labeled beta-cells in nude rats and follow their distribution and mass by MRI. This part of work may provide us a non-invasive imaging method for future studies of transplanted islets or insulin secreted beta-cells in encapsulated devices for treating type I diabetes. We will also develop new strategies for imaging endogenous beta-cells of pancreas in transgenic mice with a diabetic genetic background. Islets and beta-cells of these mice undergo hyperplasia. The increased islet number/size will be advantageous for MRI detection. We will explore new methods for the selective labeling of beta-cells of pancreas, including selectively expressing molecular markers on beta-cells of transgenic mice, and applying beta novel class of beta-cell specific peptides isolated by the phage display technique at UTSW. This part of work may provide us MR imaging methods for studying beta-cells in diabetic animal models, and may become a powerful research tool for characterizing beta-cells in many other transgenic mice available. Future development and application of these imaging methods may help us better understand the dynamic changes of beta-cell mass and function of pancreas during the pathogenesis of type II diabetes, and may help us monitor the effects of medical treatments on beta-cells.