S-NITROSYLATION & INFLAMMATION IN OBSTRUCTIVE SLEEP APNEA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肥胖与炎症增加、胰岛素抵抗和阻塞性睡眠呼吸暂停(OSA)有关。从长期健康的角度来看，胰岛素抵抗是这些问题中最重要的；然而，肥胖和胰岛素抵抗之间的病因联系尚未确定。有趣的是，全身S亚硝化水平的增加(在蛋白质中的半胱氨酸基团中添加一氧化氮)也与炎症和胰岛素抵抗有关，这增加了肥胖的一个主要胰岛素抵抗来源可能是通过S亚硝化增加。肥胖患者中S亚硝酸血症增加的一个原因可能是未确诊的阻塞性睡眠呼吸暂停综合征的高患病率。我们建议在肥胖和瘦青少年进行睡眠研究之前和之后检测他们的S-亚硝化血红蛋白(SNO-Hb)水平。然后，我们可以检查肥胖青少年的S亚硝化水平是否真的高于瘦削受试者。我们可以进一步测试更高水平的SNO-Hb是否与炎症和胰岛素抵抗增加相关。了解S-亚硝化在产生胰岛素抵抗中的作用有助于识别出有更高风险发展为胰岛素抵抗的儿童，因此需要早期干预。更重要的是，发现肥胖和胰岛素抵抗之间的机械联系，将有助于设计医疗干预措施，以降低胰岛素抵抗，从而降低患糖尿病的长期风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is associated with increased inflammation, insulin resistance and obstructive sleep apnea (OSA). From a long-term health standpoint, insulin resistance is the most significant of these issues; however, the etiologic link between obesity and insulin resistance has not been determined. Interestingly, increased systemic levels of S-nitrosylation (the addition of nitric oxide to cysteine moities in proteins) have also been linked to inflammation and insulin resistance, raising the possibility that a major source of insulin resistance in obesity could be via increased S-nitrosylation. One source of increased S-nitrosylation in obesity might be the high prevalence of undiagnosed OSA. We propose to test for levels of S-nitrosylated hemoglobin (SNO-Hb) among obese and lean adolescents before and after they undergo sleep studies. We can then examine whether levels of S-nitrosylation are indeed higher among obese adolescents vs. lean subjects. We can further test whether higher levels of SNO-Hb correlate with increased inflammation and insulin resistance. Knowledge of the role of S-nitrosylation in the production of insulin resistance could help in identifying children at increased risk for developing insulin resistance who would thus require earlier intervention. More importantly, discovery into the mechanistic link between obesity and insulin resistance would be useful for designing medical interventions to decrease insulin resistance and thus long-term risks of developing diabetes.