TY - JOUR T1 - Nitric Oxide Stimulates <sup>18</sup>F-FDG Uptake in Human Endothelial Cells Through Increased Hexokinase Activity and GLUT1 Expression JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 365 LP - 370 VL - 46 IS - 2 AU - Jin-Young Paik AU - Kyung-Han Lee AU - Bong-Ho Ko AU - Yearn Seong Choe AU - Yong Choi AU - Byung-Tae Kim Y1 - 2005/02/01 UR - http://jnm.snmjournals.org/content/46/2/365.abstract N2 - The endothelium constitutes a functionally active organ critically involved in angiogenesis. Nitric oxide (NO) is an important regulator of vascular homeostasis and angiogenesis and stimulates glucose metabolism in certain cells. We thus investigated the effect of exogenous NO on 18F-FDG transport in human endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with the NO donors sodium nitroprusside (SNP) or diethylenetriamine (DETA), in concentrations of 1 μmol/L–1 mmol/L for up to 24 h. 18F-FDG uptake levels corrected for protein content were determined by cellular radioactivity measured after 30-min incubation. Cells were evaluated for total hexokinase activity and plasma membrane glucose transporter 1 (GLUT1) levels, and involvement of potential signaling pathways was investigated by cotreatment with respective protein kinase inhibitors. Results: Both SNP and DETA stimulated HUVEC 18F-FDG uptake, which began at 16 h and peaked at 24 h. The increase in 18F-FDG uptake was dose dependent, reaching 464.0% ± 49.8% and 254.5% ± 10.8% of control levels at 24 h with 1 mmol/L SNP and DETA, respectively. Exposure of HUVECs to 1 mmol/L SNP resulted in a 3.5 ± 0.3-fold elevation in hexokinase activity (P &lt; 0.01) and a significant increase in GLUT1 levels. SNP-stimulated 18F-FDG uptake was abolished by cotreatment with cycloheximide, the tyrosine kinase inhibitor genistein, the phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin, or the protein kinase C inhibitor staurosporine. Conclusion: NO stimulates 18F-FDG uptake in HUVECs through an increase in GLUT1 expression and hexokinase activity, which appears to involve both protein kinase C and PI3K pathways. ER -