Beta-Cell Mass And Function In Implants and Pancreas

性状（由申请方提供）：胰岛β细胞通过分泌胰岛素在调节代谢中发挥重要作用。在1型糖尿病中，β细胞迅速受损或被破坏。在2型糖尿病中，β细胞似乎在很长一段时间内逐渐受损。然而，这种损伤过程的细节知之甚少，部分原因是我们没有方法在体内定位β细胞。通过引入β细胞来治疗糖尿病的尝试也在一定程度上受到细胞命运的不确定性的限制。这项拟议的技术开发项目旨在展示体内β细胞成像的新方法。我们已经合成了新型的磁共振成像（MRI）造影剂，可以在细胞内扩散并积累到高浓度。初步研究表明，标记的β细胞生长和分泌胰岛素正常响应葡萄糖。我们计划将这些标记的β细胞植入裸鼠体内，并通过MRI跟踪其分布和质量。这部分工作可能为我们提供一个非侵入性成像方法，为未来的研究移植胰岛或胰岛素分泌β细胞在封装设备治疗I型糖尿病。我们还将开发新的策略来成像具有糖尿病遗传背景的转基因小鼠中胰腺的内源性β细胞。这些小鼠的胰岛和β细胞经历增生。增加的胰岛数量/大小将有利于MRI检测。我们将探索胰腺β细胞选择性标记的新方法，包括在转基因小鼠的β细胞上选择性表达分子标记，以及应用UTSW噬菌体展示技术分离的β细胞特异性肽。这部分工作可能为我们研究糖尿病动物模型中的β细胞提供MR成像方法，并可能成为表征许多其他转基因小鼠中β细胞的强有力的研究工具。这些影像学方法的发展和应用将有助于我们更好地了解II型糖尿病发病过程中胰岛β细胞数量和功能的动态变化，并有助于我们监测药物治疗对胰岛β细胞的影响。

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.