Transendothelial glucose transport is not restricted by extracellular hyperglycaemia

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• 作者：Sarka Tumova^a ; Asimina Kerimi^a ; Karen E. Porter^b ; Gary Williamson^a ; ^{g.williamson@leeds.ac.uk}
• 关键词：AGE ; Advanced Glycation End Products ; ddPCR ; droplet digital PCR ; DHA ; docosahexaenoic acid ; EC ; endothelial cells ; eNOS ; endothelial Nitric Oxide Synthase ; GLUT ; glucose transporter ; HAoEC ; Human Aortic Endothelial Cells ; HDMEC ; Human Dermal Microendothelial Cells ; HUVEC ; Human Umbilical Vein Endothelial Cells ; Na ; K-ATPase ; Sodium Potassium ATPase ; PNGase F ; Peptide N-Glycosidase F ; PM ; plasma membrane ; RAGE ; Receptor for Advanced Glycation End Products ; SGLT ; Sodium-Glucose Linked Transporter
• 刊名：Vascular Pharmacology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：87
• 期：Complete
• 页码：219-229
• 全文大小：941 K
• 卷排序：87

文摘

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 of 14C-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, and 14C-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.