Expanded LUXendin color palette for GLP1R detection and visualization in vitro and in vivo

Julia Ast, Alissa N Novak, Tom Podewin, Nicholas H F Fine, Ben Jones, Alejandra Tomas, Ramona Birke, Kilian Roßmann, Bettina Mathes, Jenny Eichhorst, Martin Lehmann, Amelia K Linnemann, David J Hodson, Johannes Broichhagen

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Abstract

The glucagon-like peptide-1 receptor (GLP1R) is expressed in peripheral tissues and the brain, where it exerts pleiotropic actions on metabolic and inflammatory processes. Detection and visualization of GLP1R remains challenging, partly due to a lack of validated reagents. Previously, we generated LUXendins, antagonistic red and far-red fluorescent probes for specific labeling of GLP1R in live and fixed cells/tissues. We now extend this concept to the green and near-infrared color ranges by synthesizing and testing LUXendin492, LUXendin551, LUXendin615, and LUXendin762. All four probes brightly and specifically label GLP1R in cells and pancreatic islets. Further, LUXendin551 acts as a chemical beta cell reporter in preclinical rodent models, while LUXendin762 allows noninvasive imaging, highlighting differentially accessible GLP1R populations. We thus expand the color palette of LUXendins to seven different spectra, opening up a range of experiments using wide-field microscopy available in most labs through super-resolution imaging and whole animal imaging. With this, we expect that LUXendins will continue to generate novel and specific insights into GLP1R biology.

Original languageEnglish
Pages (from-to)1007-1017
Number of pages11
JournalJACS Au
Volume2
Issue number4
Early online date4 Apr 2022
DOIs
Publication statusPublished - 25 Apr 2022

Bibliographical note

© 2022 The Authors. Published by American Chemical Society.

Keywords

  • GLP1R
  • beta cell
  • diabetes
  • fluorescent probes
  • incretin
  • noninvasive imaging

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