A mechanistic examination of the metabolic regulation of insulin resistance, sarcopenia, and osteoporosis

dc.contributor.advisorMelinda Sheffield-Moore, Ph.D.en_US
dc.contributor.committeeMemberRandall J. Urban, M.D.en_US
dc.contributor.committeeMemberKevin R. Short, Ph.D.en_US
dc.contributor.committeeMemberConcepcion Diaz-Arrastia, M.D.en_US
dc.contributor.committeeMemberBlake B. Rasmussen, Ph.D.en_US
dc.creatorEdgar Lichar Dillonen_US
dc.date.accessioned2011-12-20T16:05:33Z
dc.date.available2008-06-17en_US
dc.date.available2011-12-20T16:05:33Z
dc.date.created2007-11-17en_US
dc.date.issued2007-11-14en_US
dc.description.abstractAging is associated with a number of physiological changes, including increased risk of insulin resistance and type 2 diabetes mellitus (T2DM), decreased muscle mass and strength, and decreased bone mass and bone mineral density (BMD). The aim of the studies presented were to investigate 1) the kinetics of glucose-derived breath CO2 between drug naïve impaired glucose tolerant (IGT) and normal glucose tolerant (NGT) individuals following an oral glucose load, 2) the effects of chronic oral supplementation of essential amino acids (EAA) on the acute muscle protein synthetic response to an oral bolus of EAA in older men and women, and 3) the effects of continuous and monthly cycled administration of testosterone on markers of bone metabolism in older men with low normal endogenous testosterone production.\r\nStudy 1) During a 10-h oral glucose tolerance test, blood and breath samples were collected following ingestion of 75 g of glucose isotopically labeled with 150 mg of U-13C6-Glucose. Glucose-derived breath 13CO2 was lower in IGT as compared to NGT from 1 to 3.5 h post-glucose (P&#8804;0.05). Glucose-derived breath CO2 kinetics measured during the immediate post-glucose ingestion period may assist in recognition of undiagnosed IGT in at-risk individuals during the pre-diabetes stage of T2DM.\r\nStudy 2) Older men and women received daily between-meal supplements of either 7.5 g EAA (LO), 15 g EAA (HI), or placebo (PL) for three months. Chronic EAA supplementation increased net phenylalanine uptake in the leg of LO and HI (P<0.05) without altering the magnitude of the acute FSR or total and phosphorylated Akt, mTOR, S6K1 or 4E-BP1 response. The magnitude of the anabolic response to an oral EAA ingestion in healthy older men and women remains intact after 3 months of EAA supplementation.\r\nStudy 3) Older men received continuous weekly testosterone injections for 5 months (TE), monthly cycled testosterone treatment (MO) or weekly placebo (PL). Continuous weekly testosterone administration resulted in decreased serum n-telopeptide (NTX) and serum osteocalcin (OC) in TE. Continuous testosterone treatment results in a decrease in both bone resorption and bone formation in older men.en_US
dc.format.mediumelectronicen_US
dc.identifier.otheretd-11172007-141458en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/261
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.subjectmuscle atrophyen_US
dc.subjectglucose toleranceen_US
dc.subjectbone lossen_US
dc.subjectagingen_US
dc.titleA mechanistic examination of the metabolic regulation of insulin resistance, sarcopenia, and osteoporosisen_US
dc.type.genredissertationen_US
dc.type.materialtexten_US
thesis.degree.departmentCell Biologyen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhDen_US

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