title: Hypoxia-induced increases in glucose uptake do not cause oxidative injury or advanced glycation end-product (AGE) formation in vascular endothelial cells.
abstract: An increase in glucose uptake by endothelial cells exposed to hyperglycemia is the presumed initiating event that causes systemic vascular disease in individuals with diabetes. Diabetics do not develop clinically significant pulmonary vascular disease, however, despite the pulmonary circulation's exposure to the same level of glucose. We hypothesized that pulmonary artery endothelial cells are protected from the detrimental effects of hyperglycemia because they take up less glucose than endothelial cells in the systemic circulation, either because of intrinsic differences between the two cell types or because the lower oxygen tension in the pulmonary arterial blood depresses glucose uptake. To test this hypothesis, we exposed normoglycemic and hyperglycemic bovine pulmonary artery (PAECs) and aortic endothelial cells (AECs) from the same animal to progressively lower oxygen tensions and determined glucose uptake. In contrast with our initial hypothesis, we detected no significant difference in glucose uptake between the two cell types. Furthermore, glucose uptake in both PAECs and AECs increased, not decreased, as the oxygen tension dropped; this oxygen-dependent increase in glucose uptake in endothelial cells predominated over the hyperglycemia-mediated decrease in glucose uptake that has been reported by others. Despite the increase in glucose uptake at lower oxygen tensions, we detected no corresponding increase in protein carbonylation or advanced glycation endproducts. These results demonstrate that small physiologically relevant changes in oxygen tension can have an important impact on glucose uptake in endothelial cells. These results also demonstrate that an increase in glucose uptake, by itself, is not sufficient to generate ROS-mediated protein carbonylation or increase intracellular advanced glycation endproducts in vascular endothelial cells.
authors.affiliation: The Center for Lung Biology, University of South Alabama School of Medicine, Mobile, Alabama, USA The Department of Pharmacology, University of South Alabama School of Medicine, Mobile, Alabama, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Viator
authors.affiliation: The Center for Lung Biology, University of South Alabama School of Medicine, Mobile, Alabama, USA The Department of Pharmacology, University of South Alabama School of Medicine, Mobile, Alabama, USA Department of Pharmacology, Zarqa University, Zarqa, Jordan.
authors.forename: Heba
authors.initials: H
authors.lastname: Khader
authors.affiliation: The Center for Lung Biology, University of South Alabama School of Medicine, Mobile, Alabama, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Hingorani
authors.affiliation: The Center for Lung Biology, University of South Alabama School of Medicine, Mobile, Alabama, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Long
authors.affiliation: The Center for Lung Biology, University of South Alabama School of Medicine, Mobile, Alabama, USA The Department of Pharmacology, University of South Alabama School of Medicine, Mobile, Alabama, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Solodushko
authors.affiliation: The Center for Lung Biology, University of South Alabama School of Medicine, Mobile, Alabama, USA The Department of Pharmacology, University of South Alabama School of Medicine, Mobile, Alabama, USA The Department of Internal Medicine/Division of Pulmonary and Critical Care Medicine, University of South Alabama School of Medicine, Mobile, Alabama, USA bfouty@health.southalabama.edu.
authors.forename: Brian
authors.initials: B
authors.lastname: Fouty
keywords: Advanced glycation endproducts; diabetes; endothelial cells; glucose; glucose transporter; pulmonary circulation