Feng-Hao Geng1, Guo-Hua Li1, Xing Zhang1, Peng Zhang2, Ming-Qing Dong3, Zhi-Jing Zhao4, Yuan Zhang1, Ling Dong1, Feng Gao1,4. 1. School of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China. 2. Department of Orthopedic Surgery, Urumqi General Hospital, Urumqi, China. 3. Department of Pathophysiology, The Fourth Military Medical University, Xi'an, China. 4. Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Abstract
BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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)). KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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. LINKED ARTICLES: 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.
BACKGROUND AND PURPOSE: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 diabeticrats. EXPERIMENTAL APPROACH: Diabetes was induced in male Sprague–Dawley rats by feeding a high-fat diet and administration of a low dose of streptozotocin. These diabeticrats 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)). KEY RESULTS:Berberine treatment for 4 weeks significantly restored the impaired ACh- and insulin-induced vasodilatation of mesenteric arteries from diabeticrats. 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. CONCLUSIONS AND IMPLICATIONS: Berberine improves diabetic vascular insulin sensitivity and mesenteric vasodilatation by up-regulating insulin receptor-mediated signalling in diabeticrats. These findings suggest berberine has potential as a preventive or adjunctive treatment of diabetic vascular complications. LINKED ARTICLES: 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: Wenguang Chang; Ming Zhang; Jing Li; Zhaojie Meng; Shengnan Wei; Hongwei Du; Li Chen; Grant M Hatch Journal: Metabolism Date: 2013-03-26 Impact factor: 8.694