Figure 13.

Absorption and localization of semaglutide in dog gastric mucosa. (A) Local 3F15 (semaglutide) immunofluorescence reactivity (red) under the tablet. Nuclei counterstained with 4′,6-diamidino-2-phenylindole (DAPI; blue). Scale bar, 2 mm. (B) 3F15 reactivity (red) restricted to the neck region. The bulk of H₊/K₊ ATPase (green)–positive parietal cells reside in deeper layers, but a few scattered parietal cells can be found in the neck region exposed to luminal semaglutide. Scale bar, 200 μm. (C) 3F15 (red), β-catenin (purple), ZO1 (green), and DAPI (blue). Sloughing of the uppermost region of the epithelium is marked by white asterisks; semaglutide is also detected in deeper, intact layers (white box). Scale bar, 200 μm. (D) Higher magnification of the boxed area in (C). Intact tight junctions labeled with apical ZO1 (green) in direct contact with luminal semaglutide. Scale bar, 40 μm. (E) Same region as (D) without β-catenin. Intracellular 3F15 reactivity (red) is observed in mucosal cells (marked by white arrows). 3F15 also detects semaglutide in capillaries under the epithelium (marked by white asterisks). Scale bar, 40 μm. (F) Maximum projection image from a 63 × confocal 11-μm z stack, showing semaglutide (red) associated with a blood vessel (marked by white arrows) labeled with smooth muscle actin (green). Scale bar, 40 μm. From Buckley et al. (262). Reprinted with permission from the American Association for the Advancement of Science (AAAS).