Caffeic acid phenethyl amide improves glucose homeostasis and attenuates the progression of vascular dysfunction in Streptozotocin-induced diabetic rats

Cardiovascular Diabetology

Original Investigation

An-Sheng Lee¹  Tzong-Cherng Chi²  Yi-Jin Ho³  Ching-Chia Chang Chien³  Ming-Jai Su³  Wen-Pin Chen³  Yueh-Hsiung Kuo⁴  Hsi-Lin Chiu⁴ 

[1] Department of Medicine, Mackay Medical College, New Taipei, Taiwan;Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan;Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan;Tsuzuki Institute for Traditional Medicine, China Medical University, Taichung, Taiwan;

关键词: Diabetes;    Vascular dysfunction;    Caffeic acid phenethyl amide;   

DOI  :  10.1186/1475-2840-12-99

 received in 2013-04-16, accepted in 2013-06-30,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundGlucose intolerance and cardiovascular complications are major symptoms in patients with diabetes. Many therapies have proven beneficial in treating diabetes in animals by protecting the cardiovascular system and increasing glucose utilization. In this study, we evaluated the effects of caffeic acid phenethyl amide (CAPA) on glucose homeostasis and vascular function in streptozotocin (STZ)-induced type 1 diabetic rats.MethodsDiabetes (blood glucose levels > 350 mg/dL), was induced in Wistar rats by a single intravenous injection of 60 mg/kg STZ. Hypoglycemic effects were then assessed in normal and type 1 diabetic rats. In addition, coronary blood flow in Langendorff-perfused hearts was evaluated in the presence or absence of nitric oxide synthase (NOS) inhibitor. The thoracic aorta was used to measure vascular response to phenylephrine. Finally, the effect of chronic treatment of CAPA and insulin on coronary artery flow and vascular response to phenylephrine were analyzed in diabetic rats.ResultsOral administration of 0.1 mg/kg CAPA decreased plasma glucose in normal (32.9 ± 2.3% decrease, P < 0.05) and diabetic rats (11.8 ± 5.5% decrease, P < 0.05). In normal and diabetic rat hearts, 1–10 μM CAPA increased coronary flow rate, and this increase was abolished by 10 μM NOS inhibitor. In the thoracic aorta, the concentration/response curve of phenylephrine was right-shifted by administration of 100 μM CAPA. Coronary flow rate was reduced to 7.2 ± 0.2 mL/min at 8 weeks after STZ-induction. However, 4 weeks of treatment with CAPA (3 mg/kg, intraperitoneal, twice daily) started at 4 weeks after STZ induction increased flow rate to 11.2 ± 0.5 mL/min (P < 0.05). In addition, the contractile response induced by 1 μM phenylephrine increased from 6.8 ± 0.6 mN to 11.4 ± 0.4 mN (P < 0.05) and 14.9 ± 1.4 mN (P < 0.05) by insulin (1 IU/kg, intraperitoneal) or CAPA treatment, respectively.ConclusionsCAPA induced hypoglycemic activity, increased coronary blood flow and vascular response to phenylephrine in type 1 diabetic rats. The increase in coronary blood flow may result from endothelial NOS activation. However, the detailed cellular mechanisms need to be further evaluated.

【 授权许可】

Unknown   
© Ho et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.