S-NITROSYLATION & INFLAMMATION IN OBSTRUCTIVE SLEEP APNEA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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，S-亚硝基化（将一氧化氮添加到蛋白质中的半胱氨酸部分）的全身水平增加也与炎症和胰岛素抵抗有关，提高了肥胖症胰岛素抵抗的主要来源可能是通过增加S-亚硝基化的可能性。 肥胖症中S-亚硝基化增加的一个来源可能是未诊断的OSA的高患病率。我们建议测试水平的S-亚硝基血红蛋白（SNO-Hb）之间的肥胖和瘦青少年之前和之后，他们接受睡眠研究。 然后，我们可以检查S-亚硝基化水平是否确实在肥胖青少年中高于瘦受试者。 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-亚硝基化在胰岛素抵抗产生中的作用有助于识别胰岛素抵抗风险增加的儿童，从而需要早期干预。 更重要的是，发现肥胖和胰岛素抵抗之间的机制联系将有助于设计医疗干预措施，以减少胰岛素抵抗，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.