CYP2J3 Gene Delivery Reduces Insulin Resistance via Upregulation of eNOS in Fructose-treated Rats

Cardiovascular Diabetology

Original Investigation

Luyun Wang¹  Xizhen Xu²  Ling Tu²  Dao Wen Wang²  Xiaosai Fang² 

[1] Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120, Guangzhou, People's Republic of China;Department of Internal Medicine and The Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People's Republic of China;

关键词: Nitric Oxide;    Insulin Resistance;    Fructose;    eNOS Expression;    Improve Insulin Resistance;   

DOI  :  10.1186/1475-2840-10-114

 received in 2011-10-04, accepted in 2011-12-21,  发布年份 2011

来源: Springer

【 摘 要 】

Accumulating evidence suggests that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs) which play important roles in various pathophysiological processes. Interestingly, CYP-derived eicosanoids are vasodilatory, at least in part through their ability to activate eNOS and subsequent NO release. This study investigated the roles of eNOS in CYP2J3 gene delivery reducing blood pressure and improving insulin resistance in fructose-treated rats. CYP2J3 overexpression in vivo increased EET generation, reduced blood pressure and reversed insulin resistance as determined by insulin resistance index (HOMA-IR). Furthermore, administration of eNOS inhibitor L-NMMA significantly and partially abolished the beneficial effects of CYP2J3 gene delivery on hypertension and insulin resistance induced by fructose intake, and possible mechanism is associated with increased ET-1, ETA-receptor mRNA expression and reduced sensitivity of insulin to peripheral tissues and organs characterized by reduced activity of IRS-1/PI3K/AKT and AMPK signalling pathways. These data provide direct evidence that CYP2J3-derived EETs may alleviate insulin resistance at least in part through upregulated eNOS expression.

【 授权许可】

Unknown   
© Xu et al; licensee BioMed Central Ltd. 2011. 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.