Oral Semaglutide Preserves Islet of Langerhans Structure and Cellular Integrity in a Type 2 Diabetes Mellitus Rat Model: Histological, Immunohistochemical, and Biochemical Study

Background Semaglutide (SEMA) is a promising glucagon-like peptide-1 receptor agonists (GLP-1 RAs) that is widely used in diabetes mellitus (DM). Aim In the current study, we assessed effect of oral SEMA on the cellular aspect of the islets of Langerhans along with its effect on the glucose hemostasis as well as lipid profile. Materials & Methods Forty male albino wistar rats were randomly assigned into four groups (n = 10 each): control, type 2 diabetes mellitus (T2 DM), smeglutide (SEMA), and T2DM+ SEMA. T2DM was induced by a single intraperitoneal injection of streptozotocin (27.5 mg/kg) combined with a high fat diet. Diabetes was confirmed by fasting blood glucose ≥ 160 mg/dl. Semaglutide (0.23 mg/kg/day, orally) was administrated for 21 days. At the end of the experiment, pancreatic tissue was dissected, sectioned and processed for hematoxylin and eosin, toluidine blue, Masson trichrome and immunohistochemical staining. Results Diabetic rats exhibited significant reduction in islet size. β -cell mass, insulin immunoreactivity and ki-67 positive cells, accompanied by increased α-cell distribution (P < 0.05). Semaglutide treatment significantly restored islet morphology, β -cell mass, insulin expression and β -cell proliferation, while returning α-cell distribution to near- control levels. Conclusion Oral semaglutide preserved the structural and cellular integrity of the islets of Langerhans in type 2 diabetic rats by restoring islet architecture, marinating β -cell mass, enhancing β -cell proliferating activity, and normalizing α-cell distribution.