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Effects of Blood Glucose Elevation on the Structure and Function of Microvascular Networks of Skeletal Muscle in Mice

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dc.contributor.advisor Frame, Mary D. en_US
dc.contributor.author Georgi, Melissa Katherine-Barrell en_US
dc.contributor.other Department of Biomedical Engineering en_US
dc.date.accessioned 2012-05-15T18:03:40Z
dc.date.accessioned 2015-04-24T14:45:28Z
dc.date.available 2012-05-15T18:03:40Z
dc.date.available 2015-04-24T14:45:28Z
dc.date.issued 2010-05-01
dc.identifier Georgi_grad.sunysb_0771E_10123.pdf en_US
dc.identifier.uri http://hdl.handle.net/1951/55434 en_US
dc.identifier.uri http://hdl.handle.net/11401/70995 en_US
dc.description.abstract Diabetes Mellitus and its precursor, pre-diabetes, are metabolic disorders that are characterized by high levels of elevated blood glucose. This work addresses the effects of these diseases on the microvasculature of the peripheral cardiovascular system including endothelial dysfunction and capillary rarefaction, which lead to circulation problems and secondary complications. The purpose of this study is to develop an understanding of the arteriolar network architecture and function in peripheral skeletal muscle in the normal mouse and to investigate the effects of alterations in blood glucose. We demonstrate that only two hours of elevated glucose concentration decreases dilatory responses in both endothelium dependent and endothelium independent pathways in normal mice. Additionally, two hours elevation of glucose concentration shows early evidence of shear dysregulation in the networks. To investigate the effects of chronic full-blow diabetes, two leptin-challenged models of metabolic syndrome were used. Baseline non-fasting blood glucose differs between strains; The ob/ob mice had an elevated non-fasting blood glucose level as compared with the wild type mice, and the diabetic mice had an extremely elevated non-fasting blood glucose level. Architecture was significantly different in the metabolic models. Total network length was decreased in the db/db model and increased in the ob/ob model as compared to C57 animals. C57 and ob/ob animals had a similar number of bifurcations per network, while the db/db animals had fewer. The feed diameter of the db/db mice were significantly smaller than normal C57 mice overall when bifurcation sequence was not taken into account. Additionally, when analyzed by bifurcation sequence, the db/db strain had significantly smaller diameters (feed and branch) than both the C57 and the ob/ob mice at only the first bifurcation. Changes in cytokine expression are distinct between the three mouse strains which may be related to architecture. Patterns in blood flow and flux are altered in the metabolic models as compared to metabolically normal mice. These data suggest that a brief elevation in glucose has effects that may be related to the significant changes in structure and function seen in the metabolically challenged models of diabetes. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Engineering, Biomedical -- Biology, Physiology en_US
dc.subject.other diabetes, microcirculation, shear stress, vascular architecture en_US
dc.title Effects of Blood Glucose Elevation on the Structure and Function of Microvascular Networks of Skeletal Muscle in Mice en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Helmut Strey en_US
dc.contributor.committeemember Peter Brink en_US
dc.contributor.committeemember Mohammad Kiani. en_US

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