Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA.
Mol Cell Proteomics. 2022 Dec;21(12):100426. doi: 10.1016/j.mcpro.2022.100426. Epub 2022 Oct 14.
Despite their diminutive size, islets of Langerhans play a large role in maintaining systemic energy balance in the body. New technologies have enabled us to go from studying the whole pancreas to isolated whole islets, to partial islet sections, and now to islet substructures isolated from within the islet. Using a microfluidic nanodroplet-based proteomics platform coupled with laser capture microdissection and field asymmetric waveform ion mobility spectrometry, we present an in-depth investigation of protein profiles specific to features within the islet. These features include the islet-acinar interface vascular tissue, inner islet vasculature, isolated endocrine cells, whole islet with vasculature, and acinar tissue from around the islet. Compared to interface vasculature, unique protein signatures observed in the inner vasculature indicate increased innervation and intra-islet neuron-like crosstalk. We also demonstrate the utility of these data for identifying localized structure-specific drug-target interactions using existing protein/drug binding databases.
尽管胰岛体积微小，但它们在维持全身能量平衡方面起着重要作用。新技术使我们能够从研究整个胰腺发展到分离完整胰岛、部分胰岛切片，现在甚至可以从胰岛内部分离出胰岛亚结构。我们使用基于微流控纳升液滴的蛋白质组学平台，结合激光捕获显微切割和现场非对称波形离子迁移谱，深入研究了胰岛内特定特征的蛋白质图谱。这些特征包括胰岛-腺泡界面血管组织、胰岛内部血管、分离的内分泌细胞、带有血管的完整胰岛以及胰岛周围的腺泡组织。与界面血管相比，在内部血管中观察到的独特蛋白质特征表明，神经支配增加和胰岛内神经元样细胞间通讯增加。我们还展示了这些数据在使用现有蛋白质/药物结合数据库识别局部结构特异性药物靶点相互作用方面的应用。
