Transendothelial glucose transport is not restricted by extracellular hyperglycaemia.
Endothelial cells are routinely exposed to elevated glucose concentrations post-prandially in healthy individuals and permanently in patients with metabolic syndrome and diabetes, and so we assessed their sugar transport capabilities in response to high glucose. In human umbilical vein (HUVEC), saphenous vein, microdermal vessels and aorta, GLUT1 (SLC2A1), GLUT3 (SLC2A3), GLUT6 (SLC2A6), and in microdermal vessels also GLUT12 (SLC2A12), were the main glucose transporters as assessed by mRNA, with no fructose transporters nor SGLT1 (SLC5A1). Uptake of14C-fructose was negligible. GLUT1 and GLUT3 proteins were detected in all cell types and were responsible for ~60% glucose uptake in HUVEC, where both GLUT1 and GLUT3, but not GLUT6 siRNA knock-down, reduced the transport. Under shear conditions, GLUT1 protein decreased, GLUT3 increased, and14C-deoxy-glucose uptake was attenuated. In high glucose, lipid storage was increased, cell numbers were lower,14C-deoxy-glucose uptake decreased owing to attenuated GLUT3 protein and less surface GLUT1, and trans-endothelial transport of glucose increased due to cell layer permeability changes. We conclude that glucose transport by endothelial cells is relatively resistant to effects of elevated glucose. Cells would continue to supply it to the underlying tissues at a rate proportional to the blood glucose concentration, independent of insulin or fructose.
Faculty of Mathematics and Physical Sciences, University of Leeds, Leeds LS29JT, UK.
Sarka
S
Tumova
Faculty of Mathematics and Physical Sciences, University of Leeds, Leeds LS29JT, UK.
Asimina
A
Kerimi
Leeds Institute of Cardiovascular and Metabolic Medicine, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds LS29JT, UK.
Karen E
KE
Porter
Faculty of Mathematics and Physical Sciences, University of Leeds, Leeds LS29JT, UK. Electronic address: g.williamson@leeds.ac.uk.
Gary
G
Williamson
D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology / Q000378:metabolism
D051246:Glucose Transport Proteins, Facilitative; D012333:RNA, Messenger; D005632:Fructose; D005947:Glucose
Diabetes; Endothelial cell; Glucose transport; Hyperglycaemia; Shear stress