SMOKING CESSATION, INTRAMUSCULAR TRIGLYCERIDE, AND INSULIN ACTION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。吸烟使个人面临患心血管疾病和糖尿病的风险。研究表明，吸烟会降低荷尔蒙胰岛素将血糖转化为身体组织的能力。这种对胰岛素的抵抗增加了吸烟者患糖尿病的风险，然而，吸烟如何使人对胰岛素产生抵抗的细节尚不清楚。肌肉中储存的脂肪可能是促进骨骼肌对胰岛素抵抗的一个重要因素。随着肌肉储存更多的脂肪，它对胰岛素的抵抗力变得更强。这项研究的目的是确定吸烟和戒烟对肌肉中储存的脂肪代谢和胰岛素正常工作的能力的影响。目前，人们对肌肉中储存的脂肪及其与吸烟者疾病的关系知之甚少。慢性吸烟者有几种代谢变化，可能会使肌肉储存更多的脂肪。这些变化包括脂肪细胞向血液中释放脂肪的速度增加，以及血液中脂肪浓度的增加。这些变化似乎是由烟草烟雾中的尼古丁暴露所介导的。据报道，吸烟者的脂肪摄取量增加，肌肉中的脂肪作为燃料使用不变。吸烟者脂肪细胞吸收更多脂肪的能力降低，肌肉吸收脂肪的能力没有变化。这些代谢变化可能会改变脂肪在体内的储存位置，促进肌肉的储存。肌肉脂肪含量增加与胰岛素正常工作能力降低之间的关系尚不清楚。吸烟者胰岛素正常工作的能力下降可能会受到肌肉脂肪使用变化的影响。减少肌肉脂肪的使用可能会使肌肉脂肪转化为其他类型的脂肪，从而降低肌肉对胰岛素的反应。我们计划在一个帮助人们戒烟的项目前后研究非吸烟者和吸烟者，以确定吸烟是否会增加肌肉脂肪的含量及其使用。我们希望通过确定肌肉中可能阻止肌肉对胰岛素产生反应的因素的变化，来更好地了解为什么胰岛素在吸烟者身上不起作用。受试者将在戒烟后的不同时间进行测试，以确定胰岛素正常工作的能力，以及肌肉脂肪使用的减少胰岛素作用的产物是否同时发生变化。我们认为，与不吸烟的人相比，长期吸烟者的肌肉脂肪含量增加，肌肉脂肪的使用量减少。肌肉脂肪使用的这些变化可能会增加肌肉脂肪产物的形成，从而阻止肌肉对胰岛素的反应。研究结果对预防和治疗吸烟者的胰岛素抵抗综合征、心血管疾病和糖尿病等多种疾病和状况具有广泛的意义。这些数据还将提供更完整的了解胰岛素在吸烟者中的作用方式，以更好地定制未来的治疗干预措施。如果我们的预测是正确的，这项研究还可能指导未来的研究，以调查目前未诊断的疗法的好处，以提高胰岛素在无法戒烟以预防心血管疾病和糖尿病的吸烟者中的效果。

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. Cigarette smoking puts individuals at risk for the development of cardiovascular disease and diabetes. Smoking has been shown to decrease the ability of the hormone insulin to work in disposing of blood sugar into body tissues. This resistance to insulin increases the risk of diabetes in smokers, however the details of how smoking makes people resistant to insulin is not well understood. Lipid stored in muscle may be an important factor promoting resistance to insulin in skeletal muscle. As muscle stores more lipid it becomes more resistant to insulin. The purpose of the studies in this grant is to determine the effects of smoking and stopping smoking on the metabolism of lipid stored in muscle and the ability of insulin to work properly. Currently, little is known about lipid stored in muscle and how this may be related to disease in smokers. There are several metabolic changes in chronic smokers which may make muscle store more lipid. These changes include increased rate at which fat cells release fat into the blood, and an increase in the concentration of fat in the blood. These changes appear to be mediated by nicotine exposure from tobacco smoke. Increased fat uptake, and unchanged fat use as a fuel in muscle have also been reported in smokers. Smokers also have a decreased ability of fat cells to take up more fat and unchanged ability of muscle to take up fat. These metabolic changes may alter where fat is stored in the body promoting storage in muscle. How increased muscle fat content is related to a decreased ability of insulin to work properly is not well understood. The decreased ability of insulin to work properly in smokers may be influenced by changes in muscle fat use. Decreased use of muscle fat may allows muscle fat to be converted to other types of lipid which makes muscle less responsive to insulin. We are planning to study non-smokers and smokers before and after a program to help people stop smoking to determine if smoking increases muscle fat content and its use. We hope to better understand why insulin doesn't work well in smokers by determining changes in factors in muscle which may keep muscle from responding to insulin. Subjects will be tested at different times after stopping smoking to determine if the ability of insulin to work properly, and products of muscle fat use which decrease insulin action change at the same time. We think chronic smokers have increased content of fat in muscle, and decreased muscle fat use relative to non-smokers. These changes in muscle fat use may increase formation of products from muscle fat which prevents muscle from responding as well to insulin. Results from the proposed studies have broad meaning for the prevention and treatment of several diseases and conditions including the insulin resistance syndrome, cardiovascular disease, and diabetes in smokers. These data will also provide more complete understanding of how insulin works in smokers to better tailor future therapeutic interventions. If our predictions are correct, this study may also direct future research to investigate benefits of currently undiagnosed therapies to increase how well insulin works in smokers who are unable to stop smoking to prevent cardiovascular disease and diabetes.