THE EFFECT OF PRIOR EXERCISE ON THE FATTY ACID-INDUCED IMPAIRMENT IN INSULIN SEN

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。与肥胖相关的代谢紊乱，如胰岛素抵抗，是一个主要的健康问题。如果不及时治疗，许多肥胖者会发展为2型糖尿病，其中胰岛素抵抗是主要症状。肥胖的人血液中的脂肪含量过高，骨骼肌对脂肪的吸收也过高，这与胰岛素抵抗的发展有因果关系。例如，当精瘦、健康的人血液中的脂肪含量增加到与肥胖人群相似的水平时，就会出现胰岛素抵抗。单次锻炼会在锻炼后的数小时到数天内增加胰岛素敏感性，这种影响在肥胖中保留下来，尽管其机制尚不完全清楚。到目前为止，还没有研究调查运动对脂肪引起的胰岛素敏感性降低的影响。为了做到这一点，我们将检查瘦（体重指数< 25 kg/m2）健康女性（18-45岁）在脂肪输注期间的胰岛素敏感性，在受试者保持久坐或进行单次运动后的早晨。此外，我们将评估单次运动如何影响肌肉内脂肪的储存和氧化，以及参与脂肪代谢的基因和蛋白质的表达。受试者将按随机顺序进行两项试验。我们假设，运动能够预防由脂肪可用性增加引起的胰岛素抵抗，这种预防将与肌肉中脂肪储存和氧化能力的变化同时发生。确定单次运动对高脂肪可用性引起的胰岛素抵抗的影响是很重要的，因为它将为运动改善肥胖患者胰岛素敏感性的机制提供有价值的信息。最终，这可能会改善与肥胖有关的疾病（如糖尿病）的治疗和/或药物治疗。

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 related metabolic disorders, such as insulin resistance, are a major health problem. If untreated, many obese individuals will develop Type 2 diabetes, of which insulin resistance is a primary symptom. Obese individuals have excessive availability of fat in their blood and uptake by the skeletal muscle, which has been causally linked with the development of insulin resistance. For example when the availability of fat in the blood is increased in lean, healthy people to levels similar to those found in obesity, insulin resistance occurs. A single session of exercise increases insulin sensitivity for hours to days after exercise, and this effect is preserved in obesity, although the mechanisms are not completely understood. To date no study has investigated the effect of exercise on the fat-induced reduction in insulin sensitivity. To do this we will examine insulin sensitivity during a fat infusion in lean (body mass index < 25 kg/m2), healthy females (18-45 yrs), the morning after subjects have either remained sedentary or performed a single session of exercise. Also, we will assess how a single session of exercise affects the storage and oxidation of fat within the muscle as well as the expression of genes and proteins involved in fat metabolism. Subjects will perform both trials in a randomized order. We hypothesize that exercise will be able prevent insulin resistance that is caused by increased fat availability and that this prevention will occur in parallel with changes in the ability to store and oxidize fat within the muscle. Determining the effects of a single session of exercise on insulin resistance that is caused by high fat availability is important, as it will provide valuable information regarding the mechanisms whereby exercise improves insulin sensitivity in obesity. Ultimately this could lead to improvements in the therapeutic and/or pharmacological treatment of obesity-related diseases such as diabetes.