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Angiotensin II‐induced insulin resistance in skeletal muscle by activation of nuclear factor kB via NADPH oxidase.
Author(s) -
Wei Yongzhong,
Sowers James R.,
Clark Suzanne E,
Ferrario Carlos M,
Stump Craig S
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a663-b
Subject(s) - nadph oxidase , glut4 , angiotensin ii , chemistry , medicine , insulin resistance , reactive oxygen species , endocrinology , skeletal muscle , valsartan , insulin , receptor , biology , biochemistry , blood pressure
It has been shown that reactive oxygen species (ROS) derived from NADPH oxidase mediate Angiotensin II (Ang II)‐induced insulin resistance in skeletal muscle cells. To further investigate the molecular mechanisms, transgenic Ren‐2 rat exhibiting increased tissue Ang II levels and cell cultures were utilized. ROS, NF‐κB activation, and TNF‐α were increased in soleus muscles from Ren‐2 compared Sprague‐Dawley rats, and these were attenuated and insulin sensitivity was restored in soleus muscles from Ren‐2 rats treated with angiotensin II type 1 receptor blocker valsartan or ROS scavenger tempol. Ang II induced significantly increase of NF‐κB nuclear translocation, TNF‐α production, NADPH oxidase activity, and gp91 phox expression with an impaired insulin‐mediated GLUT4 translocation to the sarcolemma in L6 myotubes. Valsartan, antioxidant N‐acetylcysteine, and specific NADPH oxidase inhibitor (gp91ds‐tat peptide) each inhibited Ang II‐induced NADPH oxidase activation, ROS production, NF‐κB nuclear translocation, and TNF‐α generation, while restoring GLUT4 translocation. Furthermore, MG132, a NF‐κB inhibitor, prevented Ang II‐induced NF‐κB activation and TNF‐α production, restored GLUT4 translocation. These suggest that NF‐κB activation by NADPH oxidase may be an important mediator of Ang II‐induced insulin resistance in skeletal muscle.