Beta-Cell Mass And Function In Implants and Pancreas

描述（申请人提供）：朗格汉斯胰岛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细胞很快被破坏或破坏。在2型糖尿病中，β细胞似乎在较长时间内逐渐受损。然而，这种损伤过程的细节尚不清楚，部分原因是我们没有方法在体内定位β细胞。通过引入β细胞治疗糖尿病的尝试也受到限制，部分原因是细胞命运的不确定性。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。我们已经合成了一种新的磁共振成像（MRI）造影剂，它可以在细胞内扩散并积聚到高浓度。初步研究表明，作为对葡萄糖的反应，标记β细胞生长并正常分泌胰岛素。我们计划将这些标记的β细胞植入裸鼠，并通过MRI跟踪其分布和质量。这部分工作可能为我们未来研究移植胰岛或胰岛素分泌β细胞的封装装置治疗I型糖尿病提供一种无创成像方法。我们还将开发具有糖尿病遗传背景的转基因小鼠胰腺内源性β细胞成像的新策略。这些小鼠的胰岛和β细胞发生增生。增大的胰岛数量/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新型β细胞特异性肽。这部分工作为我们研究糖尿病动物模型中的β细胞提供了磁共振成像方法，并可能成为表征其他转基因小鼠β细胞的有力研究工具。这些成像方法的未来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腺β细胞质量和功能的动态变化，并有助于我们监测药物治疗对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.