Proteomic Profiling of Intra-Islet Features Reveals Substructure-Specific Protein Signatures |
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Institution: | 1. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA;2. Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA;3. Belharra Therapeutics San Diego County, California, USA;4. Pfizer Worldwide Research and Development, La Jolla, California, USA;5. Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA |
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Abstract: | 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. |
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Keywords: | pancreatic islet laser capture microdissection nanoPOTS intra-islet microvasculature drug-target interaction ABC"} {"#name":"keyword" "$":{"id":"kwrd0045"} "$$":[{"#name":"text" "_":"ammonium bicarbonate FAIMS"} {"#name":"keyword" "$":{"id":"kwrd0055"} "$$":[{"#name":"text" "_":"high-field asymmetric waveform ion mobility spectrometry LCM"} {"#name":"keyword" "$":{"id":"kwrd0065"} "$$":[{"#name":"text" "_":"laser capture microdissection nanoPOTS"} {"#name":"keyword" "$":{"id":"kwrd0075"} "$$":[{"#name":"text" "_":"nanodroplet processing in one-pot for trace samples |
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