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Insulin release, membrane potential and intra-cellular Ca were studied using the pancreatic <jats:italic>\u03b2<\/jats:italic>-cell line, BRIN-BD11 and primary mouse pancreatic islets. Cellular glucose-uptake\/insulin action by 3T3-L1 adipocytes, starch digestion, glucose diffusion, dipeptidyl peptidase-4 (DPP-IV) activity and glycation were determined together with <jats:italic>in vivo<\/jats:italic> studies assessing glucose homoeostasis in high-fat-fed (HFF) rats. Active phytoconstituents with insulinotropic activity were isolated using reversed-phase HPLC, LCMS and NMR. A hot water extract of <jats:italic>C. sinensis<\/jats:italic> increased insulin secretion in a concentration-dependent manner. Insulinotropic effects were significantly reduced by diazoxide, verapamil and under Ca-free conditions, being associated with membrane depolarisation and increased intra-cellular Ca<jats:sup>2+<\/jats:sup>. Insulin-releasing effects were observed in the presence of KCl, tolbutamide and isobutylmethylxanthine, indicating actions beyond K<jats:sup>+<\/jats:sup> and Ca<jats:sup>2+<\/jats:sup> channels. The extract also increased glucose uptake\/insulin action in 3T3L1 adipocyte cells and inhibited protein glycation, DPP-IV enzyme activity, starch digestion and glucose diffusion. Oral administration of the extract enhanced glucose tolerance and insulin release in HFF rats. Extended treatment (250 mg\/5 ml per kg orally) for 9 d led to improvements of body weight, energy intake, plasma and pancreatic insulin, and corrections of both islet size and <jats:italic>\u03b2<\/jats:italic>-cell mass. These effects were accompanied by lower glycaemia and significant reduction of plasma DPP-IV activity. Compounds isolated by HPLC\/LCMS, isoquercitrin and rutin (464\u00b72 Da and 610\u00b73 Da), stimulated insulin release and improved glucose tolerance. These data indicate that <jats:italic>C. sinensis<\/jats:italic> leaves warrant further evaluation as an effective adjunctive therapy for T2DM and source of bioactive compounds.<\/jats:p>","DOI":"10.1017\/s0007114520005085","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T17:04:21Z","timestamp":1608224661000},"page":"1149-1163","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":29,"title":["Anti-hyperglycaemic and insulin-releasing effects of <i>Camellia sinensis<\/i> leaves and isolation and characterisation of active compounds"],"prefix":"10.1017","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9474-2766","authenticated-orcid":false,"given":"Prawej","family":"Ansari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Harriott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-3419","authenticated-orcid":false,"given":"Yasser H. 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