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Glibenclamide was used as a reference antidiabetic drug. Forty-eight adult male Wistar rats were used along the study and divided equally into 6 groups of (I) normal control, (II) chitosan-encapsulated selenium nanoparticles (CTS-SeNPs), (III) glibenclamide, (IV) streptozotocin (STZ), (V) STZ\u2009+\u2009CTS-SeNPs, and (VI) STZ\u2009+\u2009Glib. The animals were sacrificed on the 35th day of the experiment. Serum glucose, insulin, IGF-1, ALT, AST, CK-MB, oxidative stress, lipid profile, and inflammatory parameters were subsequently assessed. Also, the expression level of TCF7L2, CAPN10, and PPAR-\u03b3 genes were evaluated using qPCR. In addition, histopathological studies on pancreatic tissue were carried out. The results revealed that STZ induced both diabetes and oxidative stress in normal rats, manifested by the significant changes in the studied parameters and in the physical structure of pancreatic tissue. Oral administration of CTS-SeNPs or Glib results in a significant amelioration of the levels of serum fasting blood glucose, insulin, IGF-1, AST, ATL, and CK-MB as compared with STZ-induced diabetic rats. CTS-SeNPs and Glib diminished the level of lipid peroxidation, increased total antioxidant capacity level, as well as possessed strong inhibition against serum \u03b1-amylase and \u03b1-glucosidase activities. Diabetic animals received CTS-SeNPs, or Glib demonstrated a significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) decrease in the expression level of TCF7L2 and CAPN10 genes with a significant increase in the expression level of PPAR-\u03b3 gene, compared to STZ group. The above findings clarify the promising antidiabetic and antioxidant effect of CTS-SeNPs, recommending its inclusion in the currently used protocols for the treatment of diabetes and in the prevention of its related complications.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s12011-022-03140-7","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T21:08:19Z","timestamp":1646255299000},"page":"306-323","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Chitosan-Encapsulated Nano-selenium Targeting TCF7L2, PPAR\u03b3, and CAPN10 Genes in Diabetic Rats"],"prefix":"10.1007","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0759-6279","authenticated-orcid":false,"given":"Omayma A. 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