The Relationship Between Elevations in Glucocorticoids and Diabetes Development in Rats on Skeletal Muscle Insulin Resistance and the Microvasculature

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dc.contributor.advisorRiddell, Michael C.
dc.creatorDunford, Emily
dc.date.accessioned2016-11-25T14:13:53Z
dc.date.available2016-11-25T14:13:53Z
dc.date.copyright2016-05-09
dc.date.issued2016-11-25
dc.date.updated2016-11-25T14:13:53Z
dc.degree.disciplineKinesiology & Health Science
dc.degree.levelDoctoral
dc.degree.namePhD - Doctor of Philosophy
dc.description.abstractElevations in GC concentrations are well-known to cause a variety of negative systemic side effects, and subtle alterations in GC secretion and tissue-specific actions are a possible link between insulin resistance, the metabolic syndrome and T2DM development. These pathological conditions impair insulin-stimulated skeletal muscle blood flow and glucose uptake, in addition to causing profound myopathy, all of which could be significant contributors to the metabolic complications associated with insulin resistance. The focus of this dissertation was to understand how elevations in GC concentrations can be associated with skeletal muscle insulin resistance and diabetes development and whether augmentation to the muscle microvasculature is beneficial or even possible during conditions that generate significant exposure to elevations in GCs. To examine these situations, two rodent models of diabetes were used; exogenous elevations in GCs either combined with a HFD or provided a standard chow diet, to reproduce T2DM, and STZ-treated rats to induce -cell destruction, simulating T1DM. As both regular exercise and circulating insulin levels have been well documented in the regulation of microvascular augmentation, we assessed the therapeutic potential of voluntary exercise and pharmacologically enhancing hyperemia in both GC-induced skeletal muscle insulin resistance and STZ-induced diabetes. We revealed that the skeletal muscle is severely altered (decreased glycolytic muscle insulin-stimulated glucose transport and considerable glycolytic fibre atrophy) in the presence of hypercortisolemia coupled with HFD, but these alterations could be attenuated with the administration of voluntary aerobic exercise. The hypercortisolemia also resulted in alterations to the microvasculature (capillary rarefaction), which, when attenuated through 1-antagonism, produced a correlative enhancement in insulin sensitivity. Finally, the combination of voluntary exercise and 1-antagonism, in a model of chemically-induced (STZ) diabetes, demonstrated synergistic qualities through the increase in capillary growth within both glycolytic and oxidative skeletal muscle and enhanced glycemic control. This thesis provides considerable evidence proving that manipulation of the skeletal muscle microvasculature, either through voluntary exercise or pharmacologically enhanced hyperemia, can attenuate the hypercortisolemia-induced skeletal muscle capillary rarefaction and improve glucose metabolism through enhanced glucose uptake and insulin sensitivity.
dc.identifier.urihttp://hdl.handle.net/10315/32757
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectKinesiology
dc.subject.keywordsGlucocorticoids
dc.subject.keywordsSkeletal muscle
dc.subject.keywordsCapillaries
dc.subject.keywordsRat
dc.subject.keywordsHigh-fat diet
dc.subject.keywordsAtrophy
dc.subject.keywordsCorticosterone
dc.subject.keywordsCortisol
dc.titleThe Relationship Between Elevations in Glucocorticoids and Diabetes Development in Rats on Skeletal Muscle Insulin Resistance and the Microvasculature
dc.typeElectronic Thesis or Dissertation

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