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In this study, we found that<jats:italic>C. edulis<\/jats:italic>extract (CE) is protective against diabetes in mice. The treatment of hyperglycemic and hyperlipidemic apolipoprotein E (ApoE)\u2212\/\u2212 mice with a high dose of CE reduced serum glucose by 28.84% and serum total cholesterol by 17.34% and increased insulin release. We also found that CE significantly enhanced insulin secretion in a glucose-independent manner in hamster pancreatic \u03b2 cell (HIT-T15). Further investigation revealed that CE stimulated insulin exocytosis by a protein kinase C (PKC)-dependent signaling pathway and that CE selectively activated novel protein kinase Cs (nPKCs) and atypical PKCs (aPKCs) but not conventional PKCs (cPKCs) in HIT-T15 cells. To the best of our knowledge, our study is the first to identify the PKC pathway as a direct target and one of the major mechanisms underlying the antidiabetic effect of CE. Given the good insulinotropic effect of this herbal medicine, CE is a promising agent for the development of new drugs for treating diabetes.<\/jats:p>","DOI":"10.1038\/srep40454","type":"journal-article","created":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T11:23:47Z","timestamp":1484565827000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Corydalis edulis Maxim. 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