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Recent clinical studies have shown that berberine reduces blood pressure and increases systemic insulin sensitivity in patients with metabolic syndrome; however, the underlying mechanism is still unclear. Here, we investigated the mechanism by which berberine improves vascular insulin sensitivity in diabetic rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Diabetes was induced in male Sprague\u2013Dawley rats by feeding a high\u2010fat diet and administration of a low dose of streptozotocin. These diabetic rats were treated with berberine (200\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, gavage) for 4\u00a0weeks. Vascular dilation was determined in isolated mesenteric artery rings. Effects of berberine on insulin signalling were also studied in human artery endothelial cells cultured in high glucose (25\u00a0mmol\u00b7L<jats:sup>\u22121<\/jats:sup>) and palmitate (500\u00a0\u03bcmol\u00b7L<jats:sup>\u22121<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Berberine treatment for 4 weeks significantly restored the impaired ACh\u2010 and insulin\u2010induced vasodilatation of mesenteric arteries from diabetic rats. In isolated mesenteric artery rings, berberine (2.5\u201310\u00a0\u03bcmol\u00b7L<jats:sup>\u22121<\/jats:sup>) elicited dose\u2010dependent vasodilatation and significantly enhanced insulin\u2010induced vasodilatation. Mechanistically, berberine up\u2010regulated phosphorylation of the insulin receptor and its downstream signalling molecules AMPK, Akt and eNOS, and increased cell viability and autophagy in cultured endothelial cells. Moreover, down\u2010regulating insulin receptors with specific siRNA significantly attenuated berberine\u2010induced phosphorylation of AMPK.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Berberine improves diabetic vascular insulin sensitivity and mesenteric vasodilatation by up\u2010regulating insulin receptor\u2010mediated signalling in diabetic rats. These findings suggest berberine has potential as a preventive or adjunctive treatment of diabetic vascular complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/bph.2015.172.issue-23\">http:\/\/dx.doi.org\/10.1111\/bph.2015.172.issue-23<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13466","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T01:53:07Z","timestamp":1456451587000},"page":"1569-1579","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Berberine improves mesenteric artery insulin sensitivity through up\u2010regulating insulin receptor\u2010mediated signalling in diabetic rats"],"prefix":"10.1111","volume":"173","author":[{"given":"Feng\u2010Hao","family":"Geng","sequence":"first","affiliation":[{"name":"School of Aerospace Medicine The Fourth Military Medical University  Xi\u2018an 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