Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice.
Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice.
复制标题
CYP2J3 表达增加可降低果糖治疗大鼠和 db/db 小鼠的胰岛素抵抗
作者：
Xu X;Zhao CX;Wang L;Tu L;Fang X;Zheng C;Edin ML;Zeldin DC;Wang DW
目的细胞色素P450（CYP）表氧化酶将花生四烯酸（AA）代谢为环氧二十碳三烯酸（E3），E3在心血管稳态中起着重要而多样的作用。依普利的抗炎、抗高血压和促增殖作用表明依普利对胰岛素抵抗和糖尿病可能具有有益作用。研究设计和方法本研究调查了CYP 2 J3表氧化酶基因治疗对糖尿病db/db小鼠和果糖诱导的高血压和胰岛素抵抗大鼠模型的胰岛素抵抗和血压的影响。结果CYP 2 J3基因在体内可增加EET的产生，降低血压，逆转胰岛素抵抗，如血糖水平、稳态模型评估胰岛素抵抗指数和葡萄糖耐量试验所确定。此外，CYP 2 J3治疗可防止果糖诱导的肝脏、肌肉、心脏、肾脏和主动脉中胰岛素受体信号传导和AMP活化蛋白激酶（AMPKs）磷酸化的降低。因此，CYP 2 J3的过表达通过激活胰岛素受体和AMPK途径保护外周组织免受糖尿病和胰岛素抵抗。结论：这些结果突出了EET系统在糖尿病和胰岛素抵抗中的有益作用。
OBJECTIVE Accumulating evidence suggests that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play crucial and diverse roles in cardiovascular homeostasis. The anti-inflammatory, antihypertensive, and pro-proliferative effects of EETs suggest a possible beneficial role for EETs on insulin resistance and diabetes. RESEARCH DESIGN AND METHODS This study investigated the effects of CYP2J3 epoxygenase gene therapy on insulin resistance and blood pressure in diabetic db/db mice and in a model of fructose-induced hypertension and insulin resistance in rats. RESULTS CYP2J3 gene delivery in vivo increased EET generation, reduced blood pressure, and reversed insulin resistance as determined by plasma glucose levels, homeostasis model assessment insulin resistance index, and glucose tolerance test. Furthermore, CYP2J3 treatment prevented fructose-induced decreases in insulin receptor signaling and phosphorylation of AMP-activated protein kinases (AMPKs) in liver, muscle, heart, kidney, and aorta. Thus, overexpression of CYP2J3 protected against diabetes and insulin resistance in peripheral tissues through activation of insulin receptor and AMPK pathways. CONCLUSIONS These results highlight the beneficial roles of the CYP epoxygenase-EET system in diabetes and insulin resistance.
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影响因子：
19.6
作者：
Singh, Anurag Kumar;Amlal, Hassane;Soleimani, Manoocher
通讯作者：
Soleimani, Manoocher
影响因子：
4.8
作者：
Li, Guolian;Barrett, Eugene J.;Liu, Zhenqi
通讯作者：
Liu, Zhenqi
影响因子：
20.1
作者：
Campbell, WB;Gebremedhin, D;Harder, DR
通讯作者：
Harder, DR
影响因子：
13.6
作者：
Reungjui, Sirirat;Roncal, Carlos A.;Nakagawa, Takahiko
通讯作者：
Nakagawa, Takahiko
DOI：
10.1152/ajprenal.00221.2004
发表时间：
2005-06-01
影响因子：
4.2
作者：
Satoh, M;Fujimoto, S;Kashihara, N
通讯作者：
Kashihara, N