Bédard S, Marcotte B, Marette A
Department of Physiology, Laval University Hospital Research Center, Ste-Foy, Québec, Canada.
Diabetologia. 1998 Dec;41(12):1523-7. doi: 10.1007/s001250051100.
Recent studies have shown that cytokines and endotoxins impair insulin-stimulated glucose transport by activating the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production in skeletal muscle cells. In this study, we investigated whether iNOS induction is modulated by insulin in L6 myocytes. Long term exposure of muscle cells to tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) greatly increased iNOS mRNA expression and NO production. Addition of insulin to the cytokine/LPS-treated muscle cells reduced (by approximately 40%) NO production. This inhibition was similar to that observed with the synthetic glucocorticoid dexamethasone, a known inhibitor of iNOS in several cell types. The combination of insulin and dexamethasone was more effective than either agent alone in reducing NO production. Dexamethasone greatly inhibited the effect of cytokines/LPS to induce cellular iNOS mRNA expression. In strong contrast, insulin failed to reduce iNOS mRNA expression under similar conditions. These results show that insulin is a novel inhibitor of iNOS-mediated NO production in skeletal muscle cells. Furthermore, our data indicate that unlike glucocorticoids, insulin does not inhibit NO production by suppression of iNOS gene transcription.
近期研究表明，细胞因子和内毒素可通过激活诱导型一氧化氮合酶（iNOS）的表达以及骨骼肌细胞中一氧化氮（NO）的生成，损害胰岛素刺激的葡萄糖转运。在本研究中，我们调查了胰岛素是否在L6肌细胞中调节iNOS的诱导。将肌肉细胞长期暴露于肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和脂多糖（LPS）中，可显著增加iNOS mRNA表达和NO生成。向经细胞因子/LPS处理的肌肉细胞中添加胰岛素可降低（约40%）NO生成。这种抑制作用与合成糖皮质激素地塞米松（已知在几种细胞类型中iNOS的抑制剂）所观察到的抑制作用相似。胰岛素和地塞米松联合使用在降低NO生成方面比单独使用任何一种药物更有效。地塞米松极大地抑制了细胞因子/LPS诱导细胞iNOS mRNA表达的作用。与之形成强烈对比的是，在类似条件下胰岛素未能降低iNOS mRNA表达。这些结果表明，胰岛素是骨骼肌细胞中iNOS介导的NO生成的新型抑制剂。此外，我们的数据表明，与糖皮质激素不同，胰岛素不是通过抑制iNOS基因转录来抑制NO生成。
