The interaction between glucose and fat metabolism and insulin resistance in severely burned children and the metabolic effects of fenofibrate

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dc.contributor.advisorRobert R. Wolfeen_US
dc.contributor.committeeMemberRandall Urbanen_US
dc.contributor.committeeMemberLynis Dohmen_US
dc.contributor.committeeMemberKarl Andersonen_US
dc.contributor.committeeMemberDavid Chinkesen_US
dc.contributor.committeeMemberAsle Aarslanden_US
dc.creatorMelanie Cree Greenen_US
dc.date.accessioned2011-12-20T16:05:20Z
dc.date.available2008-06-17en_US
dc.date.available2011-12-20T16:05:20Z
dc.date.created2005-09-13en_US
dc.date.issued2005-08-09en_US
dc.description.abstractInsulin resistance occurs in conjunction with disturbances in fat and glucose metabolism and mitochondrial dysfunction. Four human studies were conducted to better understand this relationship in the settings of aging and burn trauma. \r\nThe first two studies focused on aging. Insulin resistance commonly occurs in aging, but it was unknown if this was accompanied by changes in fat metabolism. The first study examined tissue fat in healthy young and elderly in relation to insulin sensitivity. The second study attempted to decrease insulin sensitivity by increasing the mitochondrial oxidation rate of intracellular fat, and lower plasma lipids with the peroxisome proliferator activating receptor alpha agonist fenofibrate. \r\nThe final two studies focused on burn trauma in children. Children who experience severe flame burn rapidly develop insulin resistance and hyper-metabolic fat, protein and glucose regulation. This insulin resistance has been linked to increases in mortality and morbidities such as infection and delayed wound healing. It is hypothesized that the insulin resistance and metabolic dysregulation develop cumulatively for several weeks following a burn and that treatment between weeks 1 and 3 post-burn with fenofibrate will increase lipid oxidation and improve insulin sensitivity, as compared to changes seen in placebo treated children. Study three examined glucose kinetics including a) whole body glucose uptake during a hyperinsulinemic-euglycemic clamp, b) endogenous glucose production, c) glucose uptake across the leg and d) fasting glucose and insulin levels measured at 1 and 3 weeks post-burn, before and after treatment. Additionally, lipid kinetics, as reflected by a) free fatty acid oxidation b) fatty acid release c) intracellular triglyceride in the liver and muscle, and intracellular diacyglycerol and fatty acyl CoA were measured at these time points. Finally, the activity of the insulin signaling pathway in muscle was also measured, as was mitochondrial function. The last study served to quantitate the level of mitochondrial dysfunction following burn, by comparing the mitochondrial function in the burn trauma patients to that in healthy children. \r\n \r\n\r\nen_US
dc.format.mediumelectronicen_US
dc.identifier.otheretd-09132005-131026en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/227
dc.language.isoengen_US
dc.rightsCopyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.en_US
dc.subjectinsulin resitanceen_US
dc.subjectglucose metabolsimen_US
dc.subjectfat metabolsimen_US
dc.subjectburn traumaen_US
dc.subjectagingen_US
dc.titleThe interaction between glucose and fat metabolism and insulin resistance in severely burned children and the metabolic effects of fenofibrateen_US
dc.type.genredissertationen_US
dc.type.materialtexten_US
thesis.degree.departmentPreventive Medicine and Community Healthen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhDen_US

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