Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium

Guzman-Gutierrez, Enrique, Armella, Axel, Toledo, Fernando, Pardo, Fabian, Leiva, Andrea and Sobrevia, Luis (2015) Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium. Purinergic Signalling, 12 1: 175-190. doi:10.1007/s11302-015-9491-2


Author Guzman-Gutierrez, Enrique
Armella, Axel
Toledo, Fernando
Pardo, Fabian
Leiva, Andrea
Sobrevia, Luis
Title Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium
Journal name Purinergic Signalling   Check publisher's open access policy
ISSN 1573-9546
1573-9538
Publication date 2015-12-28
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s11302-015-9491-2
Open Access Status Not yet assessed
Volume 12
Issue 1
Start page 175
End page 190
Total pages 16
Place of publication Dordrecht, Netherlands
Publisher Springer
Language eng
Formatted abstract
Gestational diabetes mellitus (GDM) associates with increased L-arginine transport and extracellular concentration of adenosine in human umbilical vein endothelial cells (HUVECs). In this study we aim to determine whether insulin reverses GDM-increased L-arginine transport requiring adenosine receptors expression in HUVECs. Primary cultured HUVECs from full-term normal (n = 38) and diet-treated GDM (n = 38) pregnancies were used. Insulin effect was assayed on human cationic amino acid transporter 1 (hCAT1) expression (protein, mRNA, SLC7A1 promoter activity) and activity (initial rates of L-arginine transport) in the absence or presence of adenosine receptors agonists or antagonists. A1 adenosine receptors (A1AR) and A2AAR expression (Western blot, quantitative PCR) was determined. Experiments were done in cells expressing or siRNA-suppressed expression of A1AR or A2AAR. HUVECs from GDM exhibit higher maximal transport capacity (maximal velocity (V max)/apparent Michaelis Menten constant (K m), V max/K m), which is blocked by insulin by reducing the V max to values in cells from normal pregnancies. Insulin also reversed the GDM-associated increase in hCAT-1 protein abundance and mRNA expression, and SLC7A1 promoter activity for the fragment −606 bp from the transcription start point. Insulin effects required A1AR, but not A2AAR expression and activity in this cell type. In the absence of insulin, GDM-increased hCAT-1 expression and activity required A2AAR expression and activity. HUVECs from GDM pregnancies exhibit a differential requirement of A1AR or A2AAR depending on the level of insulin, a phenomenon that represent a condition where adenosine or analogues of this nucleoside could be acting as helpers of insulin biological effects in GDM.
Keyword Diabetes
Insulin
Adenosine receptor
Fetal
Endothelium
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
 
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