Proteomic Profiling of Intra-Islet Features Reveals Substructure-Specific Protein Signatures

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. Graphical Abstract Highlights • We differentiated intra-islet substructures by their proteome profiles in situ.• We demonstrated significant functional differences between vasculature types.• Novel differences in innervation and colocalization of nerves were observed.• We demonstrated a depth of coverage useful for predictive binding discovery assays.• We identified pathways with these techniques that could aid drug characterizations. In Brief Improved sample handling techniques have enabled us to go from studying the whole pancreas, to isolated whole islets, to islet sections, and now to islet substructures isolated from within islet sections. 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 from intra-islet features. The protein coverage and expression profiles obtained are sufficient to fully distinguish each of these features while presenting their own unique proteome signatures.

SUBMITTER: Swensen A 

PROVIDER: S-EPMC9706166 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature