Hypoxia upregulates GLUT‐1 expression in rat pulmonary endothelial cells even in hyperglycemia

Abstract

Hyperglycemia is common in critical illness and is associated with worse outcome. Why this occurs is not clear. Glucose entry into endothelial cells occurs mainly through the sodium‐independent, non‐insulin regulated, glucose transporter 1 (GLUT‐1). The level of GLUT‐1 expression is a key determinant of how much glucose enters endothelial cells. Hyperglycemia decreases GLUT‐1 expression, whereas hypoxia and inflammation increase expression. In critical illness, where hyperglycemia, hypoxia and inflammation are all present, the net effect on GLUT‐1 expression in pulmonary artery endothelial cells is unknown. Cultured Rat Pulmonary Artery Endothelial Cells (RPAECs) were exposed to hypoxia (5% O2) and either high (20 mmol) or low (5 mmol) glucose, and GLUT‐1 protein expression was determined. Hypoxia (5% oxygen) increased GLUT‐1 protein expression in RPAECs in both high (20 mmol) and low (5 mmol) glucose based on Western blot analysis and immunocytochemistry. Additionally, the hypoxia‐induced upregulation of GLUT‐1 correlated with increased glucose uptake. In conclusion, hypoxia upregulates GLUT‐1 even in hyperglycemia and increases glucose uptake in RPAECs. This may be important in understanding the detrimental effects of hyperglycemia in critical illness. [This work is supported by funding from the NIH/NHLBI grant HL073244 and the NIH training grant HL076125.]