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Effect of Sodium Salicylate on Insulin Resistance and Endothelial Dysfunction of Coronary Arterioles in Diabetic Mice
Author(s) -
Yang Jiyeon,
Park Yoonjung,
Zhang Cuihua
Publication year - 2008
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.22.2_supplement.45
Subject(s) - insulin resistance , endocrinology , medicine , iκb kinase , endothelial dysfunction , sodium salicylate , insulin , insulin receptor , nf κb , inflammation
Sodium Salicylate (NaSal) has been previously reported to inhibit the activity of inhibitor kappaB (I κ B) kinase beta (IKKβ), which is required for activation of nuclear factor kappa B (NF κ B). IKKβ is induced by tumor necrosis factor alpha (TNF) and plays pivotal roles in inhibiting propagation of insulin signaling transduction. Accordingly, we hypothesized that NaSal may restore both endothelial dysfunction and insulin resistance by inhibiting IKK β /NF κ B activity. We assessed the roles of NaSal in endothelial function in isolated coronary arterioles and insulin resistance in m Lepr db (heterozygote, normal) and Lepr db (type II diabetic) mice by administrating IKKβ inhibitor NaSal. Glucose level was decreased and HOMA‐Insulin Resistance and insulin tolerance test shows improved insulin sensitivity. Our Western blot results show that expression of phospho‐IKKβ, phospho‐JNK, NFκB and TNF were markedly attenuated in Lepr db mice treated with NaSal. NaSal partially restored dilation to endothelium‐dependent agonist, acetycholine (ACh) and flow in Lepr db mice, but did not affect the protein expression of nitrotyrosine (peroxinitrite (ONOO − ). Our results indicate that IKKb and JNK signaling interact to induce endothelial dysfunction and insulin resistance in Type II diabetes. An intriguing finding of this study is that the roles of IKKb appear reversed in the inflammatory response in diabetic Lepr db mice.