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Author Viator, Ryan Joseph
Title Oxygen tension controls glucose uptake and metabolism in endothelial cells
book jacket
Descript 121 p
Note Source: Dissertation Abstracts International, Volume: 71-10, Section: B, page: 5885
Adviser: Brian W. Fouty
Thesis (Ph.D.)--University of South Alabama, 2010
Hyperglycemia causes systemic endothelial dysfunction and leads to increased morbidity and mortality in diabetics. While diabetes causes subtle structural changes in the lungs of animals and humans, clinically-relevant pulmonary vascular disease is uncommon. Because the systemic and pulmonary circulations are exposed to similar circulating glucose and insulin concentrations, some other factors are likely responsible for this disparate effect. Two differences between these vascular beds are the oxygen tension and shear stress experienced by each. Systemic endothelial cells are exposed to higher oxygen tension and shear stress than endothelial cells in the pulmonary circulation. A limitation of most in vitro studies is that they are performed in static culture outside of the physiological range of oxygen tensions. The main focus of this dissertation was to determine whether differences in oxygen tension within the narrow, physiologically-relevant range could control glucose uptake and metabolism in endothelial cells. Bovine aortic endothelial cells (BAECs) and bovine pulmonary artery endothelial cells (BPAECs) were incubated in 0%, 5%, 13%, or 21% oxygen or exposed to shear stress, and glucose uptake and lactate production measured. As oxygen tension decreased, glucose uptake within both BAECs and BPAECs increased. Most of this glucose was converted to lactate. The application of shear stress to endothelial cells decreased glucose transporter-1 (GLUT-1) expression but had no effect on glucose uptake. Stable overexpression of GLUT-1 in PAECs increased glucose uptake, stimulated cell proliferation and strengthened monolayer integrity (as measured by transendothelial electrical resistance, TER), but lead to a decrease in NO production. If these cell culture findings are representative of endothelial cell behavior in vivo, it suggests that endothelial cells in the pulmonary circulation take up more glucose than endothelial cells in the systemic circulation, an effect due primarily to the lower oxygen tension in the pulmonary artery. This observation may be relevant to understanding the apparently different clinical effects of diabetes in the two vascular beds
School code: 0491
Host Item Dissertation Abstracts International 71-10B
Subject Biology, Cell
0379
Alt Author University of South Alabama
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