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.
Showing the most recent 10 out of 1065 publications
