title: Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signalling in diabetic rats.
abstract: Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose and regulating lipid metabolism. 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.
  
  
  
  Diabetes was induced in male Sprague–Dawley rats by feeding a high-fat diet and administration of a low dose of streptozotocin. These diabetic rats were treated with berberine (200 mg·kg(−1)·day(−1), gavage) for 4 weeks. 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 mmol·L(−1)) and palmitate (500 μmol·L(−1)).
  
  
  
  Berberine treatment for 4 weeks significantly restored the impaired ACh- and insulin-induced vasodilatation of mesenteric arteries from diabetic rats. In isolated mesenteric artery rings, berberine (2.5–10 μmol·L(−1)) elicited dose-dependent vasodilatation and significantly enhanced insulin-induced vasodilatation. Mechanistically, berberine up-regulated 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-regulating insulin receptors with specific siRNA significantly attenuated berberine-induced phosphorylation of AMPK.
  
  
  
  Berberine improves diabetic vascular insulin sensitivity and mesenteric vasodilatation by up-regulating insulin receptor-mediated signalling in diabetic rats. These findings suggest berberine has potential as a preventive or adjunctive treatment of diabetic vascular complications.
  
  
  
  This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23.
authors.affiliation: School of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China.
authors.forename: Feng-Hao
authors.initials: FH
authors.lastname: Geng
authors.affiliation: School of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Li
authors.affiliation: School of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Urumqi General Hospital, Urumqi, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Dong
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Zhi-Jing
authors.initials: ZJ
authors.lastname: Zhao
authors.affiliation: School of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.affiliation: School of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China.|Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D034741:RNA, Small Interfering; D001599:Berberine; D011972:Receptor, Insulin; D000109:Acetylcholine