An expanded LUXendin color palette for GLP1R detection and visualization in vitro and in vivo

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/tissue. 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 chemical beta cell reporter in preclinical rodent models, while LUXendin762 allows non-invasive 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 widefield 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 insight into GLP1R biology

¹⁸O pattern and biosynthesis of natural plant products

Oxygen atoms in plant products originate from CO2, H2O and O-2, precursors with quite different delta O-18 values. Furthermore their incorporation by different reactions implies isotope effects. On this base the resulting non-statistical O-18 distributions in natural compounds are discussed. The delta O- 18 value of cellulose is correlated to that of the leaf water, and the observed O-18 enrichment (similar to + 27 parts per thousand) is generally attributed to an equilibrium isotope effect between carbonyl groups and water. However, as soluble and heterotrophically synthezised carbohydrates show other correlations, a non-statistical O-18 distribution - originating from individual biosynthetic reactions - is postulated for carbohydrates. Similarly, the delta O-18 values of organic acids, carbonyl compounds, alcohols and esters indicate water- correlated, but individual O-18 abundances (e.g. O from acyl groups similar to + 19% above water), depending upon origin and biosyntheses. Alcoholic groups introduced by monooxygenase reactions, e.g. in sterols and phenols, show delta O-18 values near + 5 parts per thousand, in agreement with an assumed isotope fractionation factor of similar to1.02 on the reaction with atmospheric oxygen (delta O-18 = +23.5 parts per thousand). Correspondingly, a "thermodynamically ordered isotope distribution" is only observed for oxygen in some functional groups correlated to an origin from CO2 and H2O, not from O-2. The individual isotopic increments of functional groups permit the prediction of global delta O-18 values of natural compounds on the basis of their biosynthesis. (C) 2001 Published by Elsevier Science Ltd

Open Access

Asymptotics of solutions of the heat equation i