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Labeling of live and fixed islets of Langerhans with LUXendin492, LUXendin551 (CELT-111), and LUXendin615. (A) Incubation of live islets with LUXendin492, LUXendin551 (CELT-111) or LUXendin615 leads to bright staining confined to the cell membrane (scale bar = 53 μm) (n = 11–13 islets from 4 mice). (B) LUXendin492, LUXendin551 (CELT-111), and LUXendin615 signals can still be detected following formalin fixation and are co-localized with orthogonal emission from a specific monoclonal antibody against GLP1R (mAb) (scale bar = 85 μm) (n = 9–10 islets from 4 mice).
(A) Labeling of live cells with LUXendin492, LUXendin551 (CELT-111), and LUXendin615. SNAP-GLP1R:CHO-K1 cells were incubated with LUXendin492 (LUX492), LUXendin551 (CELT-111), and LUXendin615 (LUX615) before orthogonal SNAP-labeling with either cell-impermeable SBG-TMR or SBG-SiR and confocal imaging (nuclei were stained using Hoechst33342) (scale bar = 10 μm) (n = three images from experiments performed in duplicate). (B) Labeling efficiency of LUXendin492, LUXendin551 (CELT-111), and LUXendin615 in SNAP-GLP1R:CHO-K1 cells, quantified as the proportion of SNAP+/LUX+ cells (versus total SNAP-labeled cells) (n = 6 wells). (C) LUXendin492, LUXendin551 (CELT-111), and LUXendin615 label SNAP-GLP1R:INS1 832/3 but not INS1 832/3 GLP1R–/– cells. (D) Additionally, endogenous GLP1R can be visualized with LUXendin551 (CELT-111) in INS1 832/3 cells, which express the receptor at lower levels than in islets (scale bars = 10 μm).
Labeling of GLP1R in NOD mouse islets in vivo. (A) Two-photon intravital imaging schematic for visualization of the exposed intact pancreas in an 8-week-old NOD mouse. (B) Representative image collected at baseline and 5 min post-injection, showing islet vasculature and accumulation of LUXendin551 (CELT-111) at cell membranes (scale bar = 50 μm). (C) Mosaic image of externalized pancreas (scale bar = 100 μm) and the enlarged islet within this region (scale bar = 50 μm).

Our GLP1R fluorescent antagonist shows high affinity for GLP1 receptor (pIC50 = 7.2 for GLP1R) modulating the receptor by orthosteric antagonism. The efficacy and potency of LUXendin551 (CELT-111) as a GLP1R ligand was confirmed by inhibition of GLP-1-stimulated cAMP levels in SNAP-GLP1R: HEK293 cells. LUXendin551 (CELT-111) has been used in a variety of imaging applications, including widefield/confocal/2-photon microscopy in live and fixed mammalian cells and tissue, as well as anaesthetized mice.

 

More information and applications

https://doi.org/10.1021/jacsau.2c00130

LUXendin551 GLP1 receptor (GLP1R) fluorescent antagonist (551/576) (CELT-111)
For research use only

3 nmol vial that allows to prepare 30 µL of 100 µM stock solution to test GLP1R. One vial is sufficient for injecting one mouse.

Please note that the required concentration may vary depending on the specific assay design.

424,00€

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