Increased CYP2J3 Expression Reduces Insulin Resistance in Fructose-treated Rats and db/db Mice

  1. Xizhen Xu1,
  2. Chun Xia Zhao1,
  3. Luyun Wang1,
  4. Ling Tu1,
  5. Xiaosai Fang1,
  6. Changlong Zheng1,
  7. Matthew L. Edin2,
  8. Darryl C. Zeldin2 and
  9. Dao Wen Wang (dwwang{at}tjh.tjmu.edu.cn)1
  1. 1Department of Internal Medicine and The Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China
  2. 2Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709

Abstract

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, anti-hypertensive 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, insulin resistance index (HOMA-IR) and Glucose Tolerance Test (GTT). Furthermore, CYP2J3 treatment prevented fructose-induced decreases in insulin receptor signaling and phosphorylation of AMP-activated protein kinases (AMPK) 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.

Footnotes

    • Received August 27, 2009.
    • Accepted December 21, 2009.

This Article

  1. Diabetes
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