Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) offer promising regenerative therapy potential. This study compared the effects of BM-MSCs and α-tocopherol (α-Toc) on apoptosis, autophagy, β-cell function, and associated signaling pathways in a streptozotocin (STZ)-induced diabetes rat model. Additionally, it explored the entero-insular axis and PI3K/Akt signaling.

Methods: Forty adult male albino rats were divided into four groups: control, diabetic (STZ-induced, 45 mg/kg), diabetic treated with BM-MSCs, and diabetic treated with α-Toc. Blood glucose, insulin, nitric oxide (NO), and catalase (CAT) levels were measured. Pancreatic histopathology, expression of insulin, CD44, caspase-3, autophagy markers, PI3K/Akt signaling, pancreas/duodenum homeobox protein 1, and glucose-dependent insulinotropic polypeptide (GIP) were analyzed using histological and molecular techniques.

Results: Diabetic rats showed elevated glucose levels, impaired GIP expression, and partial restoration of pancreatic islets. Both BM-MSCs and α-Toc treatment improved autophagy, restored PI3K/Akt signaling, and reversed intestinal GIP expression. However, BM-MSCs demonstrated superior cytoprotective effects compared to α-Toc.

Conculsion: These findings suggest that BM-MSCs and α-Toc have therapeutic potential in type 1 diabetes by targeting autophagy, β-cell function, and entero-insular axis regulation, with BM-MSCs offering a more pronounced effect.