Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase
Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase
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DOI：
10.1161/01.cir.104.3.342
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发表时间：
2001-07-17
期刊：
影响因子：
37.8
通讯作者：
Scherrer, U
中科院分区：
文献类型：
--
作者：
Duplain, H;Burcelin, R;Scherrer, U
背景 - 胰岛素抵抗和动脉高血压相关，但潜在机制尚不清楚。内皮一氧化氮合酶 (eNOS) 在骨骼肌中表达，在骨骼肌中它可以控制代谢过程，在血管内皮中表达，在血管内皮中它调节动脉压。方法和结果 - 为了研究 eNOS 在控制胰岛素代谢作用中的作用，我们通过破坏 eNOS 编码基因来评估清醒小鼠的胰岛素敏感性。 eNOS(-/-) 小鼠患有高血压、空腹高胰岛素血症、高脂血症，并且胰岛素刺激的葡萄糖摄取比对照小鼠低 40%。 eNOS(-/-) 小鼠中的胰岛素抵抗与 NO 合成受损特别相关，因为在同样高血压的 1-kid/1-clip 小鼠（肾血管性高血压模型）中，胰岛素刺激的葡萄糖摄取是正常的。 结论 - 这些结果表明，eNOS 不仅对于控制动脉压而且对于控制葡萄糖和脂质稳态也很重要。单一基因缺陷，即 eNOS 缺陷，可能代表代谢与心血管疾病之间的联系。
Background - Insulin resistance and arterial hypertension are related, but the underlying mechanism is unknown. Endothelial nitric oxide synthase (eNOS) is expressed in skeletal muscle, where it may govern metabolic processes, and in the vascular endothelium, where it regulates arterial pressure.Methods and Results - To study the role of eNOS in the control of the metabolic action of insulin, we assessed insulin sensitivity in conscious mice with disruption of the gene encoding for eNOS. eNOS(-/-) mice were hypertensive and had fasting hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose uptake than control mice. Insulin resistance in eNOS(-/-) mice was related specifically to impaired NO synthesis, because in equally hypertensive 1-kidney/1-clip mice (a model of renovascular hypertension), insulin-stimulated glucose uptake was normal.Conclusions - These results indicate that eNOS is important for the control not only of arterial pressure but also of glucose and lipid homeostasis. A single gene defect, eNOS deficiency, may represent the link between metabolic and cardiovascular disease.