Ameliorative effects of indomethacin at different concentrations on endothelial insulin resistance through two distinct pathways

Publication date: October 2018Source: Biomedicine & Pharmacotherapy, Volume 106Author(s): Tao Xian, Yuyang Gan, Yi Lu, Mengxi Wang, Wanwan Yuan, Yumeng Zhou, Junye Chen, Kun Wang, Shaofeng Xiong, Qiren HuangAbstractIndomethacin (IDMT), a non-selective inhibitor of cycloxygenase-2 (COX-2), plays important roles in anti-inflammation and analgesia and it is commonly used to treat the patients with rheumatic and rheumatoid arthritis. Besides, various literatures reported that IDMT is a synthetic ligand of peroxisome proliferator activated receptor gamma (PPARγ). Rosiglitazone (RSG), an insulin-sensitizer, is also a synthetic ligand and applied clinically to cure the patients with type 2 diabetes mellitus. However, up to date little is known about whether IDMT ameliorates endothelial insulin resistance (IR). Accordingly, the purpose of this study is to investigate the effects of IDMT on endothelial IR and its underlying mechanism. Our present results showed that IDMT improved the endothelial IR induced by high glucose and fat concentration (HG/HF) in a concentration and time-dependent manner. Intriguingly, we further identified that 0.25 mM of IDMT noticeably induced the expression levels of PPARγ, AKT and endothelial nitric oxide synthase (eNOS) but failed to notably reverse the increases in expression levels of COX-2, inhibitory κB kinase (IKK) and tumor necrosis factor alpha (TNFα) induced by HG/HF; whereas 1.0 mM of IDMT exerted opposite effects compared with 0.25 mM...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research