Zeng G, Quon M J
Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Invest. 1996 Aug 15;98(4):894-8. doi: 10.1172/JCI118871.
Hypertension is associated with insulin-resistant states such as diabetes and obesity. Nitric oxide (NO) contributes to regulation of blood pressure. To gain insight into potential mechanisms linking hypertension with insulin resistance we directly measured and characterized NO production from human umbilical vein endothelial cells (HUVEC) in response to insulin using an amperometric NO-selective electrode. Insulin stimulation of HUVEC resulted in rapid, dose-dependent production of NO with a maximal response of approximately 100 nM NO (200,000 cells in 2 ml media; ED50 approximately 500 nM insulin). Although HUVEC have many more IGF-1 receptors than insulin receptors (approximately 400,000, and approximately 40,000 per cell respectively), a maximally stimulating dose of IGF-1 generated a smaller response than insulin (40 nM NO; ED50 approximately 100 nM IGF-1). Stimulation of HUVEC with PDGF did not result in measurable NO production. The effects of insulin and IGF-1 were completely blocked by inhibitors of either tyrosine kinase (genestein) or nitric oxide synthase (L-NAME). Wortmannin (an inhibitor of phosphatidylinositol 3-kinase [PI 3-kinase]) inhibited insulin-stimulated production of NO by approximately 50%. Since PI 3-kinase activity is required for insulin-stimulated glucose transport, our data suggest that NO is a novel effector of insulin signaling pathways that are also involved with glucose metabolism.
高血压与胰岛素抵抗状态如糖尿病和肥胖相关。一氧化氮（NO）有助于血压调节。为深入了解高血压与胰岛素抵抗之间潜在的机制，我们使用安培型NO选择性电极直接测量并表征了人脐静脉内皮细胞（HUVEC）对胰岛素反应时产生的NO。胰岛素刺激HUVEC导致NO快速、剂量依赖性产生，最大反应约为100 nM NO（2 ml培养基中200,000个细胞；ED50约为500 nM胰岛素）。尽管HUVEC的IGF-1受体比胰岛素受体多得多（分别约为每个细胞400,000个和40,000个），但最大刺激剂量的IGF-1产生的反应比胰岛素小（40 nM NO；ED50约为100 nM IGF-1）。用血小板衍生生长因子（PDGF）刺激HUVEC未导致可测量的NO产生。胰岛素和IGF-1的作用被酪氨酸激酶抑制剂（染料木黄酮）或一氧化氮合酶抑制剂（L-NAME）完全阻断。渥曼青霉素（磷脂酰肌醇3激酶[PI 3激酶]抑制剂）抑制胰岛素刺激的NO产生约50%。由于PI 3激酶活性是胰岛素刺激的葡萄糖转运所必需的，我们的数据表明NO是胰岛素信号通路的一种新效应物，这些信号通路也参与葡萄糖代谢。
