Cook Stéphane, Scherrer Urs
Department of Internal Medicine and Botnar Center for Clinical Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Fundam Clin Pharmacol. 2002 Dec;16(6):441-53. doi: 10.1046/j.1472-8206.2002.00130.x.
In the Western hemisphere, the incidence of insulin resistance and its complications has been growing rapidly and is reaching epidemic proportions. Over the past decade, evidence has accumulated, indicating that nitric oxide (NO) plays a key role in the regulation of metabolic and cardiovascular homeostasis. Defective endothelial nitric oxide synthase (eNOS) driven NO synthesis causes insulin resistance, arterial hypertension and dyslipidemia in mice, and characterizes insulin-resistant humans. On the other hand, stimulation of inducible nitric oxide synthase (iNOS) and NO overproduction in mice, may also cause metabolic insulin resistance, suggesting a Yin-Yang effect of NO in the regulation of glucose homeostasis. Here, we will review the evidence for this novel concept, and thereby provide the conceptual framework for the use of NO-delivery drugs and pharmacological agents that modulate the bioavailability of endogenously produced NO for the treatment of insulin resistance.
在西半球，胰岛素抵抗及其并发症的发病率一直在迅速上升，正达到流行程度。在过去十年中，已有大量证据表明，一氧化氮（NO）在调节代谢和心血管稳态方面发挥着关键作用。由有缺陷的内皮型一氧化氮合酶（eNOS）驱动的NO合成会导致小鼠出现胰岛素抵抗、动脉高血压和血脂异常，也是胰岛素抵抗人群的特征。另一方面，小鼠体内诱导型一氧化氮合酶（iNOS）的刺激和NO的过量产生，也可能导致代谢性胰岛素抵抗，这表明NO在调节葡萄糖稳态中存在阴阳效应。在此，我们将回顾这一新概念的证据，从而为使用NO递送药物和调节内源性产生的NO生物利用度的药物来治疗胰岛素抵抗提供概念框架。
