Morphofunctional characteristics of the pancreas in triple therapy (semaglutide + omeprazole + GABA) for type 2 diabetes mellitus

Purpose of the study . To perform a morphofunctional assessment of the pancreas following administration of a combination of semaglutide + omeprazole + gamma-aminobutyric acid in a db/db mouse model of type 2 diabetes mellitus. Materials and methods . The experiment was conducted in 16‑week-old male db/db (C57BL/KsJ-Leprdbtb) mice (n = 192), which received the following agents orally every day for 90 days: A – semaglutide, B – omeprazole, and C – gamma-aminobutyric acid. The animals were divided into eight groups: group 1 (n = 26) – diabetic control; group 2 (n = 26) – A + B + C combination; group 3 (n = 26) – A + B combination; group 4 (n = 26) – agent C; group 5 (n = 10) – C57Bl/6 mice; groups 6, 7, and 8 (n = 26 in each group) – intact animals receiving A + B + C, A + B, and C, respectively. Animals were euthanized on days 30 and 90 of the experiment. Results . Group 1 exhibited disruption of pancreatic histoarchitecture characteristic of type 2 diabetes mellitus, accompanied by increased levels of insulin (1.5‑fold), HbA1c (1.3‑fold), C-peptide (3.9‑fold), leptin (1.4‑fold), total cholesterol (1.1‑fold), and triglycerides (1.2‑fold), as well as a 2.3‑fold decrease in adiponectin levels. Results were considered statistically significant at p < 0.05. In group 2, administration of the A + B + C combination was associated with less pronounced pancreatic damage compared with all other groups. Conclusion. Morphofunctional assessment demonstrated restoration of pancreatic histoarchitecture following administration of the A + B + C combination, supporting the β-cell cytoprotective effect of this therapy. Keywords: type 2 diabetes mellitus, semaglutide, omeprazole, gamma-aminobutyric acid, pancreatic islets> < 0.05. In group 2, administration of the A + B + C combination was associated with less pronounced pancreatic damage compared with all other groups. Conclusion . Morphofunctional assessment demonstrated restoration of pancreatic histoarchitecture following administration of the A + B + C combination, supporting the β-cell cytoprotective effect of this therapy.