Fig 1: Liraglutide decreases islet 14-3-3-zeta protein expression and secretion in mouse and human islets.(A) Representative images of mouse islets immunostained for insulin (red), 14-3-3-zeta (green), and DAPI (blue) in ß cell GLP-1R WT and KO mice treated with saline (CTRL) or liraglutide (LIRA). (B) Average 14-3-3-zeta staining per islet in ß cell GLP-1R WT and KO mice. (C) Abundance of four tryptic peptides of 14-3-3-zeta identified by targeted proteomics in conditioned media samples from human islets from a single human donor [human donor 1] treated with CTRL or LIRA, measured in duplicate. Ratio of abundance of the average of four tryptic peptides LIRA/CTRL is 0.042 ± 0.073. For the peptide TAFDEAIAELDTLSEESYK, both the 2+ and 3+ charge states (z) were quantified together. (D) Representative images of human islets treated with saline or liraglutide for 24 hours. Islets were immunostained for insulin (red), 14-3-3-zeta (green), and DAPI (blue). (E) Average 14-3-3-zeta staining per islet from human donors. Data are presented as means ± SEM. n = 3 donors/mice per group. **P < 0.01 by two-factor ANOVA with Bonferroni’s posttest; ##P < 0.01 by Student’s t test. Scale bar, 20 µm.