Skip to main content
. 2020 Jan 24;11:467. doi: 10.1038/s41467-020-14309-w

Fig. 3. LUXendin645 is highly specific for the GLP1R.

Fig. 3

a Schematic showing sgRNA-targeting strategy for the production of Glp1r(GE)−/− mice. The sgRNA used targeted Glp1r and the double-strand break mediated by Cas9 lies within exon1 (capital letters); intron shown in gray. b Glp1r(GE)−/− animals harbor a single-nucleotide deletion, as shown by sequencing traces. c Body weights were similar in male 8–9 weeks old Glp1r+/+, Glp1r(GE)+/−, and Glp1r(GE)−/− littermates (n = 9 animals) (one-way ANOVA with Bonferroni’s test; F = 0.362, DF = 2). d The incretin-mimetic Exendin4(1–39) (Ex4; 10 nM) is unable to significantly potentiate glucose-stimulated insulin secretion in Glp1r(GE)−/− islets (n = 15 repeats, six animals for each genotype, three separate islet preparations) (between genotype comparisons: two-way ANOVA with Sidak’s test; F = 4.061, DF = 2) (within genotype comparisons: one-way ANOVA with Bonferroni’s post-hoc test; F = 14.57 (Glp1r+/+), 10.83 (Glp1r(GE)−/−); DF = 2). e Liraglutide (Lira) does not stimulate cAMP beyond vehicle (Veh) control in Glp1r(GE)−/− islets, measured using the FRET probe Epac2-camps (n = 25 islets for each genotype, three animals per genotype, two separate islet preparations). f cAMP area-under-the-curve (AUC) quantification showing absence of significant Liraglutide-stimulation in Glp1r(GE)-/- islets (n = 25 islets for each genotype, three animals per genotype, two separate islet preparations) (Kruskal–Wallis test with Dunn’s test; Kruskal–Wallis statistic = 31.78, DF = 2) (Box and Whiskers plot shows range and median) (representative images displayed above each bar; color scale shows min to max values as a ramp from blue to red). g LUXendin645 and GLP1R antibody labeling is not detectable in Glp1r(GE)−/− islets (scale bar = 40 µm) (n = 27 islets, five animals per genotype, three separate islet preparations). For all statistical tests, *P < 0.05, **P < 0.01 and NS, non-significant. In all cases, LUXendin645 was applied at 100 nM. Mean ± s.e.m. are shown. Source data are provided as a Source Data file.