Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes
Quantification and Three-Dimensional Imaging of the Insulitis-Induced Destruction of β-Cells in Murine Type 1 Diabetes
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DOI：
10.2337/db09-1400
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发表时间：
2010-07-01
期刊：
影响因子：
7.7
通讯作者：
Holmberg, Dan
中科院分区：
文献类型：
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作者：
Alanentalo, Tomas;Hornblad, Andreas;Holmberg, Dan
研究设计和方法-使用离体技术，光学投影断层扫描（OPT），我们对3 - 16周龄的糖尿病易感NOD和非糖尿病易感同系NOD.H-2b小鼠胰腺中胰岛炎和β细胞破坏的三维空间发展和进展进行了定量和评估。连同显示胰岛炎过程的空间动力学的结果，我们提供了在1型糖尿病的发展和进展过程中，β细胞体积分布的数据，这些数据下降到单个胰岛和整个胰腺的水平。我们的数据提供了证据，证明在疾病的后期阶段，在临床糖尿病发展的时间点附近，较大的胰岛素胰岛具有代偿性生长潜力。这与较小的胰岛相反，较小的胰岛对自身免疫攻击的抵抗力较低。我们还提供了关于胰岛炎过程本身的空间动力学的新信息，包括发病时明显的随机分布，进一步发展过程中的局部变化，以及在胰岛炎进展的后期形成类似三级淋巴器官的结构。我们的数据为遗传和环境对1型糖尿病病因学的影响的表型分析以及评估1型糖尿病的发病机制提供了强有力的工具。治疗方案的潜在效果。糖尿病59：1756-1764，2010
OBJECTIVE-The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining beta-cell volume during the progression of type 1 diabetes in the nonobese diabetic (NOD) mouse model of the disease.RESEARCH DESIGN AND METHODS-Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the three-dimensional spatial development and progression of insulitis and beta-cell destruction in pancreata from diabetes-prone NOD and non-diabetes-prone congenic NOD.H-2b mice between 3 and 16 weeks of age.RESULTS-Together with results showing the spatial dynamics of the insulitis process, we provide data of beta-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression.CONCLUSIONS-Our data provide a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes. Diabetes 59:1756-1764, 2010