Wang Qiuyan, Sun Xiaohui, Li Xiaobin, Dong Xiang, Li Peng, Zhao Li
Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Emergency Department, First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China.
Mol Med Rep. 2015 Jan;11(1):151-8. doi: 10.3892/mmr.2014.2762. Epub 2014 Oct 23.
Obstructive sleep apnea can induce chronic intermittent hypoxia (CIH) during sleep and is associated with obesity and diabetes. Resveratrol (RSV), a polyphenolic phytoalexin, can regulate glucose metabolism, thereby reducing insulin resistance. The present study aimed to assess whether RSV attenuates CIH-induced insulin resistance in rats and the underlying mechanisms. A total of 40 rats were randomly assigned into five groups: i) Control; ii) subjected to CIH only; iii) subjected to CIH and treated with 3 mg/kg/day of RSV; iv) subjected to CIH and treated with 30 mg/kg/day of RSV; v) subjected to CIH and treated with 60 mg/kg/day of RSV. All animals were sacrificed following 28 days of treatment. Subsequently, the blood and livers were harvested and blood insulin and glucose levels were measured. Levels of sirtuin (Sirt) 1, insulin receptor (InsR) and glucose transporter 2 (Glut2) in the liver were measured. RSV treatment was demonstrated to suppress weight gain and improve hepatic morphology. RSV treatment also significantly reduced the homeostasis model assessment estimate of insulin resistance of the rats exposed to CIH. This effect occurred in a dose-dependent manner. RSV significantly upregulated liver Sirt1 levels and inhibited InsR and Glut2 expression in the liver. Additionally, RSV activated the phosphorylation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and AKT. The present study demonstrates that RSV prevents CIH-induced insulin resistance in rats. Upregulation of Sirt1 and activation of PI3K/AKT signaling may be involved in this process.
阻塞性睡眠呼吸暂停可在睡眠期间诱发慢性间歇性缺氧（CIH），并与肥胖和糖尿病相关。白藜芦醇（RSV）是一种多酚类植物抗毒素，可调节葡萄糖代谢，从而降低胰岛素抵抗。本研究旨在评估RSV是否能减轻CIH诱导的大鼠胰岛素抵抗及其潜在机制。总共40只大鼠被随机分为五组：i）对照组；ii）仅接受CIH；iii）接受CIH并以3 mg/kg/天的RSV治疗；iv）接受CIH并以30 mg/kg/天的RSV治疗；v）接受CIH并以60 mg/kg/天的RSV治疗。治疗28天后处死所有动物。随后，采集血液和肝脏，测量血液胰岛素和葡萄糖水平。测量肝脏中沉默调节蛋白（Sirt）1、胰岛素受体（InsR）和葡萄糖转运蛋白2（Glut2）的水平。结果表明，RSV治疗可抑制体重增加并改善肝脏形态。RSV治疗还显著降低了暴露于CIH的大鼠胰岛素抵抗的稳态模型评估值。这种作用呈剂量依赖性。RSV显著上调肝脏Sirt1水平，并抑制肝脏中InsR和Glut2的表达。此外，RSV激活了磷脂酰肌醇-4,5-二磷酸3-激酶（PI3K）和AKT的磷酸化。本研究表明，RSV可预防CIH诱导的大鼠胰岛素抵抗。Sirt1的上调和PI3K/AKT信号通路的激活可能参与了这一过程。
