{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:06:43Z","timestamp":1792444003593,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172134"],"award-info":[{"award-number":["32172134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Sci Food Agric"],"published-print":{"date-parts":[[2024,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Casein hydrolysates have attracted much interest as anti\u2010diabetic food, but their hypoglycemic mechanism and biopeptides are not well understood. This study aimed to explore the anti\u2010diabetic mechanism and potential biopeptides of casein hydrolysates in streptozotocin\/high\u2010fat\u2010diet\u2010induced diabetic rats and HepG2 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Oral administration of casein hydrolysate prepared with papain\u2013Flavourzyme combination (P\u2010FCH) decreased fasting blood glucose, improved oral glucose tolerance, and reduced HbA1c values in diabetic rats. P\u2010FCH was ineffective in alleviating insulin resistance (homeostasis model assessment and insulin sensitivity index) and enhancing hepatic insulin signaling transduction (phosphorylated Akt, hexokinase activity, and pyruvate kinase activity) in diabetic rats. However, P\u2010FCH significantly upregulated adenosine monophosphate\u2010activated protein kinase phosphorylation and glucose transporter\u20102 expression, inhibited phosphoenolpyruvate carboxylase kinase activity, and elevated glycogen content in liver tissue of diabetic rats. Furthermore, P\u2010FCH increased glucose consumption independently in normal and insulin\u2010resistant HepG2 cells without the presence of insulin. The peptide composition of P\u2010FCH was characterized. The potential biopeptides in P\u2010FCH showed the sequence characteristic of a Val at the N\u2010terminal or a Pro at the P2 position, and the hypoglycemic activity of Val\u2010Pro\u2010Leu\u2010Gly (the most potential biopeptide in P\u2010FCH) was verified by oral glucose tolerance test in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>These results suggested that activation of the non\u2010insulin\u2010mediated AMPK pathway might be the determinant mechanism of P\u2010FCH on the hypoglycemic effect. The novel peptide Val\u2010Pro\u2010Leu\u2010Gly in P\u2010FCH was effective in reducing blood glucose levels when orally administered to mice. \u00a9 2023 Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsfa.13187","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T12:00:32Z","timestamp":1701518432000},"page":"2947-2958","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Anti\u2010diabetic mechanism and potential bioactive peptides of casein hydrolysates in <scp>STZ<\/scp>\/<scp>HFD<\/scp>\u2010induced diabetic rats"],"prefix":"10.1002","volume":"104","author":[{"given":"Chenyang","family":"Wang","sequence":"first","affiliation":[{"name":"School of Food Science and Engineering South China University of Technology  Guangzhou China"},{"name":"Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center  Guangzhou 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