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While the sublingual gland (SLG) contributes to saliva production, its involvement in diabetes remains understudied. Agmatine (AGM), a naturally occurring polyamine, exhibits antioxidant and anti\u2010inflammatory properties; however, its protective effects on the SLG and pancreas in diabetes have remained largely uninvestigated. This study introduces new insights into SLG injury in diabetes and the dose\u2010dependent protective benefits of AGM through multi\u2010level analysis. Male Wistar rats were rendered diabetic by a single intraperitoneal STZ injection (65\u2009mg\/kg) and treated with either low\u2010dose (40\u2009mg\/kg) or high\u2010dose (100\u2009mg\/kg) AGM for two weeks. SLGs and the pancreas were analyzed by histological, immunohistochemical, and biochemical methods. Mucin secretion (MUC\u20105B) was measured, oxidative stress markers and pro\u2010inflammatory cytokines were quantified, and structural changes were evaluated using H&amp;E, Alcian Blue\/PAS, and Mallory's trichrome staining. Immunohistochemistry included \u03b1\u2010SMA and CK17 for SLG and insulin receptor for the pancreas. STZ\u2010induced diabetes resulted in a substantial reduction in MUC\u20105B, increased oxidative stress and pro\u2010inflammatory markers, damage to acinar and myoepithelial cells, and injury to pancreatic \u03b2\u2010cells. Agmatine administration enhanced these parameters in a dose\u2010dependent manner, with high\u2010dose treatment reinstating mucin secretion, regulating oxidative and inflammatory indicators, and maintaining histological and immunohistochemical integrity in both the sublingual gland and pancreas. AGM confers dose\u2010dependent protection against SLG dysfunction and pancreatic damage in diabetic rats via antioxidant, anti\u2010inflammatory, and cytoprotective mechanisms. These findings highlight the therapeutic potential of AGM in preventing salivary gland dysfunction and maintaining pancreatic function in diabetes.<\/jats:p>","DOI":"10.1002\/jemt.70144","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:16:33Z","timestamp":1774592193000},"page":"1158-1184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose\u2010Dependent Protective Effects of Agmatine on Sublingual Gland Dysfunction and Pancreatic Damage in Experimental Diabetes: Evidence From Histological, Biochemical, and Immunohistochemical Analyses"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-9875","authenticated-orcid":false,"given":"Heba","family":"Fikry","sequence":"first","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-9429","authenticated-orcid":false,"given":"Lobna A.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2996-4770","authenticated-orcid":false,"given":"Doaa Ramadan","family":"Sadek","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.21608\/edj.2018.77076"},{"issue":"3","key":"e_1_2_11_3_1","first-page":"1097","article-title":"The Therapeutic Effect of Honey Bee Venom Versus Mesenchymal Stem Cells on Submandibular Salivary Glands of Streptozotocin\u2010Induced Diabetic Rats","volume":"46","author":"Abd Elwahab H. 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