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This study aimed to examine and compare the ameliorative effects of BM\u2010MSCs compared to \u03b1\u2010tocopherol (\u03b1\u2010Toc) on apoptosis, autophagy, and \u03b2\u2010cell function in a rat model of streptozotocin (STZ)\u2010induced diabetes and further analyzed the implications and interrelations of the entero\u2010insular axis, and type I phosphoinositide 3\u2010kinase\u00a0(PI3K)\/Akt signaling.\u00a0Forty adult male albino rats were categorized into four groups (<jats:italic>n<\/jats:italic>\u2009=\u200910, in each): control group, STZ\u2010induced diabetic group (single i.p. injection of STZ 45\u2009mg\/kg), diabetic and treated with BM\u2010MSCs injection, diabetic and treatment with \u03b1\u2010Toc p.o. The serum glucose, insulin, nitric oxide (NO), and catalase (CAT) were measured. Histopathological examination of the pancreas, the expression levels of insulin, CD44, caspase\u20103, autophagy markers, P13K\/Akt, and pancreas\/duodenum homeobox protein 1, in pancreatic tissue, and glucose\u2010dependent insulinotropic polypeptide (GIP) in the duodenum were detected by hematoxylin and eosin staining, immunofluorescence labeling, and by quantitative real\u2010time polymerase chain reaction.\u00a0The diabetic rats showed reduced insulin, hyperglycemia, nitrosative stress (NO, CAT), augmented apoptosis (caspase 3), impaired autophagy (p62\/SQSTM1, LC3), downregulated PI3K\/Akt pathway and increased GIP expression, and degeneration of pancreatic islets. Treatment with either BM\u2010MSCs or \u03b1\u2010Toc suppressed the nitrosative stress, reduced apoptosis, recovered autophagy, upregulated PI3K\/Akt pathway, and subsequently increased insulin levels, decreased blood glucose, and downregulated GIP expression with partial restoration of pancreatic islets.\u00a0Based on our findings, the cytoprotective effects of BM\u2010MSCs and \u03b1\u2010Toc in type 1\u2010induced diabetes appeared to be related to repaired autophagy and recovered PI3K\/Akt signaling. Moreover, we reported their novel effects on reversing intestinal GIP expression level. The effect of BM\u2010MSCs was notably superior to that of \u03b1\u2010Toc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.30482","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T20:11:22Z","timestamp":1696536682000},"page":"1705-1719","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The ameliorating effects of mesenchymal stem cells compared to \u03b1\u2010tocopherol on apoptosis and autophagy in streptozotocin\u2010induced diabetic rats: Implication of PI3K\/Akt signaling pathway and entero\u2010insular axis"],"prefix":"10.1002","volume":"124","author":[{"given":"Heba A.","family":"Mubarak","sequence":"first","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine Assiut University Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manal M.","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine Assiut University Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yossra","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Faculty of Medicine Assiut University Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma S.","family":"Abd\u2010Elsamea","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine Assiut University Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eman","family":"Abdelbary","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy Al\u2010Azhar University Assiut Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa G.","family":"Gamea","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Assiut University 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