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Current Vascular Pharmacology


ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

A Role for Insulin on L-Arginine Transport in Fetal Endothelial Dysfunction in Hyperglycaemia

Author(s): Luis Sobrevia and Marcelo Gonzalez

Volume 7, Issue 4, 2009

Page: [467 - 474] Pages: 8

DOI: 10.2174/157016109789043919

Price: $65


Endothelial cells are key in the regulation of vascular tone through the release of vasoactive molecules, including nitric oxide (NO). NO is a gas synthesized from the cationic amino acid L-arginine via the endothelial NO synthase (eNOS). The semi-essential amino acid L-arginine is a taken up by endothelial cells via systems y+ and y+L in primary cultures of human umbilical vein endothelial cells (HUVEC). System y+ is a family of membrane transporters including at least five transport systems for cationic amino acids (CAT) of which HUVEC express human CAT-1 (hCAT-1) and hCAT-2B. Exposure of HUVEC to high extracellular concentrations of D-glucose increases L-arginine transport, hCAT-1 mRNA expression and eNOS activity. These phenomena are also related with increased production of reactive oxygen species (ROS), thus supporting the possibility that changes in L-arginine/NO signalling pathway result from elevated ROS. It has been shown that insulin blocks D-glucose – increased L-arginine transport and cGMP accumulation in HUVEC, whereas in this cell type insulin also modulates high D-glucose effects by activating the transcriptional factors Sp1 and NFκB. These transcription factors have response elements in SLC7A1 (for hCAT-1) gene promoter region, thus representing 2 possible targets for regulation of the expression of this transporter by D-glucose and/or insulin in this cell type. Recent evidences suggest that insulin blocks the stimulatory effect of D-glucose on L-arginine transport by reducing the transcriptional activity of SLC7A1 via Sp1-, NFκB- and ROS-dependent mechanisms. Thus, a role for these transcription factors in response to insulin is proposed in fetal endothelial cells exposed to hyperglycaemia.

Keywords: Glucose, hyperglycaemia, diabetes, L-arginine, transport, human, endothelium

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