{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T05:19:20Z","timestamp":1792387160247,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2017,7,26]],"date-time":"2017-07-26T00:00:00Z","timestamp":1501027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY17H140004"],"award-info":[{"award-number":["LY17H140004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Glucagon\u2010like peptide\u20101 (GLP\u20101) is an important target for diabetes therapy based on its key role in maintaining glucose and lipid homeostasis. This study was designed to investigate antidiabetic and hepatoprotective effects of a novel oleanolic acid derivative DKS26 in diabetic mice and elucidate its underlying GLP\u20101 related antidiabetic mechanisms <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The therapeutic effects of DKS26 were investigated in streptozotocin (STZ)\u2010induced and db\/db diabetic mouse models. Levels of plasma glucose, glycosylated serum protein (GSP), lipid profiles, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), oral glucose tolerance (OGT), pancreatic islets and hepatic histopathological morphology, liver lipid levels and expression of pro\u2010inflammatory cytokines were assessed. Intestinal NCI\u2010H716 cells and diabetic models were used to further validate its potential GLP\u20101\u2010related antidiabetic mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>DKS26 treatment (100\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> ) decreased plasma levels of glucose, GSP, ALT and AST; ameliorated OGT and plasma lipid profiles; augmented plasma insulin levels; alleviated islets and hepatic pathological morphology; and reduced liver lipid accumulation, inflammation and necrosis <jats:italic>in vivo<\/jats:italic>. Furthermore, DKS26 enhanced GLP\u20101 release and expression, accompanied by elevated levels of cAMP and phosphorylated PKA <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>DKS26 exerted hypoglycaemic, hypolipidaemic and islets protective effects, which were associated with an enhanced release and expression of GLP\u20101 mediated by the activation of the cAMP\/PKA signalling pathway, and alleviated hepatic damage by reducing liver lipid levels and inflammation. These findings firmly identified DKS26 as a new viable therapeutic option for diabetes control.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13921","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T11:32:48Z","timestamp":1497871968000},"page":"2912-2928","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Oleanolic acid derivative DKS26 exerts antidiabetic and hepatoprotective effects in diabetic mice and promotes glucagon\u2010like peptide\u20101 secretion and expression in intestinal cells"],"prefix":"10.1111","volume":"174","author":[{"given":"Fei\u2010Fei","family":"Chen","sequence":"first","affiliation":[{"name":"Experiment Education Center for Pharmaceutical Sciences, College of Pharmaceutical Sciences Zhejiang University  Hangzhou China"},{"name":"Institute of Pharmacology &amp; Toxicology, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 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