Show simple item record

dc.contributor.authorTsao, Tsu-Shuen
dc.date.accessioned2018-07-12T18:51:58Z
dc.date.available2018-07-12T18:51:58Z
dc.date.issued1997
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 58-07, Section: B, page: 3409.;Advisors: Maureen J. Charron.
dc.identifier.urihttps://yulib002.mc.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9801192
dc.identifier.urihttps://hdl.handle.net/20.500.12202/3740
dc.description.abstractThe cellular and whole body consequences of targeted overexpression of GLUT4 in two types of muscle, cardiac and fast-twitch skeletal, were examined in transgenic mice. Transgenic mice with targeted skeletal muscle overexpression of GLUT4 (MLC-GLUT4) was made using the rat myosin light chain 1/3 promoter and enhancer. Overexpression of GLUT4 resulted in increased insulin-stimulated glucose uptake and glycogen content selectively in the fast-twitch muscles. At the whole body level, insulin-stimulated glucose utilization was increased. Increased glucose flux in skeletal muscle also caused the activation of hexokinase II expression. Whether selective overexpression of GLUT4 in skeletal muscle could prevent impaired insulin action and glucose homeostasis was tested in non-obese models of insulin resistance with and without hyperglycemia and in a model of insulin resistance with obesity. Mice lacking GLUT4 (GLUT4-null) displayed impaired muscle glucose uptake and whole body insulin action, but normal glycemia. Upon introduction of the MLC-GLUT4 transgene into the GLUT4-null mice, fast-twitch muscle glucose transport and whole body insulin action were restored. Mice with heterozygous GLUT4 disruption (GLUT4 +/{dollar}-{dollar}) exhibited decreased muscle GLUT4 content, impaired muscle and whole body glucose utilization, hyperinsulinemia, and hyperglycemia. Expression of GLUT4 and glucose uptake in fast-twitch muscles were normalized by introducing the MLC-GLUT4 transgene into the GLUT4 +/{dollar}-{dollar}mice. Furthermore, expression of the MLC-GLUT4 transgene protected the GLUT4 +/{dollar}-{dollar} mice from developing hyperinsulinemia, hyperglycemia, and decreased whole body glucose utilization. Gold-thioglucose (GTG) causes obesity and insulin resistance in mice. Administration of GTG to MLC-GLUT4 mice resulted in obesity to the same extent as controls. However, development of insulin resistance following GTG injection was ameliorated in the MLC-GLUT4 mice. Transgenic mice overexpressing GLUT4 in the heart were generated using the {dollar}\alpha{dollar}-myosin heavy chain promoter. Unlike skeletal muscle, overexpression of GLUT4 in the heart did not affect whole body glucose utilization. Surprisingly, these mice exhibited decreased life span associated with cardiac hypertrophy, dilated ventricular chambers, and histopathology that include interstitial fibrosis and mural thrombus. Hemodynamic studies revealed a diminished response to inotropic challenge with elevated end diastolic pressure, indicating congestive heart failure.
dc.publisherProQuest Dissertations & Theses
dc.subjectAnimal Physiology.
dc.subjectMolecular biology.
dc.subjectBiochemistry.
dc.titleRole of muscle GLUT4 in micro- and macro-glucose homeostasis
dc.typeDissertation


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record