Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus

Pardo, Fabián; Arroyo, Pablo; Salomón, Carlos; Westermeier, Francisco; Salsoso, Rocío; Sáez, Tamara; Guzmán-Gutiérrez, Enrique; Leiva, Andrea; Sobrevía, Luis

doi:10.1016/j.placenta.2013.09.007

Cited by 22 publications

(24 citation statements)

References 66 publications

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“…In addition, these parameters showed similar correlations with the maternal concentrations of TCh (i.e., (R 2 D max /R 2 EC 50 ) TCh ¼ 1.4). Thus, a supraphysiological concentration of TCh in maternal circulation at the end of pregnancy may be detrimental for fetoplacental vasculature function [4,16,20]. However, this study was performed in vitro and may not correlate with true in utero physiological effects.…”

Section: Discussionmentioning

confidence: 96%

Cross-sectional and longitudinal lipid determination studies in pregnant women reveal an association between increased maternal LDL cholesterol concentrations and reduced human umbilical vein relaxation

et al. 2015

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Section: Discussionmentioning

confidence: 96%

Cross-sectional and longitudinal lipid determination studies in pregnant women reveal an association between increased maternal LDL cholesterol concentrations and reduced human umbilical vein relaxation

et al. 2015

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“…93 Gestational diabetes mellitus is associated with an increased incidence of both maternal and perinatal and/or neonatal morbidity, which results, at least in part, from altered vascular function that has its origins in endothelial dysfunction. 94 In the past few years, increasing attention has focused on the link between increased levels of adenosine and the onset of endothelial dysfunction in human umbilical veins during gestational diabetes mellitus. [95][96][97][98][99][100] Extracellular levels of adenosine in the culture media of primary cultures of endothelial cells of umbilical veins isolated from women with gestational diabetes mellitus are higher than those isolated from women with normal pregnancies.…”

Section: Gestational Diabetes Mellitusmentioning

confidence: 99%

Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations

et al. 2015

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Adenosine is a key extracellular signalling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors, A1, A2A, A2B and A1 adenosine receptors. Accumulating evidence highlights a critical role for the adenosine system in the regulation of glucose homeostasis and the pathophysiology of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Although adenosine signalling is known to affect insulin secretion, new data indicate that adenosine signalling also contributes to the regulation of β-cell homeostasis and activity by controlling the proliferation and regeneration of these cells as well as the survival of β cells in inflammatory microenvironments. Furthermore, adenosine is emerging as a major regulator of insulin responsiveness by controlling insulin signalling in adipose tissue, muscle and liver; adenosine also indirectly mediates effects on inflammatory and/or immune cells in these tissues. This Review critically discusses the role of the adenosine-adenosine receptor system in regulating both the onset and progression of T1DM and T2DM, and the potential of pharmacological manipulation of the adenosinergic system as an approach to manage T1DM, T2DM and their associated complications.

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“…Moreover, endothelial cells from macro-and microvasculature of different tissues differ in their ability to metabolise substrates involved in vascular tone modulation because of differential expression of genes encoding for membrane transporters for L-arginine and NO synthase [14]. Insulin and adenosine also differentially modulate different cell types because of differences in the abundance of their receptor isoforms in various tissues types [14,15]. Thus, information on macrovascular function in GDM does not necessarily apply to the microvascular environment, and functional alterations in one tissue type should not be extrapolated to another.…”

Section: Introductionmentioning

confidence: 99%

Impairments in microvascular function and skeletal muscle oxygenation in women with gestational diabetes mellitus: links to cardiovascular disease risk factors

et al. 2016

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Aims/hypothesis Gestational diabetes mellitus (GDM) is a risk factor for the development of endothelial dysfunction and cardiovascular disease. However, in vivo microvascular endothelial function in GDM has not been investigated. This study aimed to examine, using near-infrared spectroscopy (NIRS), whether: (1) there are differences in microvascular reactivity and skeletal muscle oxygen consumption (mVat rest and during exercise between GDM and uncomplicated pregnancies; and (2) ) and blunted hyperaemia (ΔTSI 6.8 ± 2.9 vs 9.5 ± 3.4) compared with controls (p < 0.01). Despite similar handgrip strength in the GDM and control groups (29.1 ± 8.1 vs 26.2 ± 10.4 kg, respectively), during repeated forearm contractions, women with GDM presented a blunted TSI response (6.5 ± 3.9 vs 19.2 ± 10.9; p < 0.01) and a reduced capacity to maintain the predetermined handgrip (23.4 ± 2.9 vs 27.4 ± 3.8%, p < 0.05). NIRS indices correlated with PWV, 24 h BP and blood glucose concentration earlier in pregnancy (r = 0.40-0.60; p < 0.05). Conclusions/interpretation Women with GDM exhibited a characteristic blunted TSI curve, showing alterations in muscle oxygenation and microvascular responsiveness compared with women with uncomplicated pregnancies. These alterations were manifested during exercise and possibly contribute to the reduced exercise tolerance in GDM. NIRS indices correlated with macrovascular indices (arterial stiffness) and 24 h BP.

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Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus

Cited by 22 publications

References 66 publications

Cross-sectional and longitudinal lipid determination studies in pregnant women reveal an association between increased maternal LDL cholesterol concentrations and reduced human umbilical vein relaxation

Cross-sectional and longitudinal lipid determination studies in pregnant women reveal an association between increased maternal LDL cholesterol concentrations and reduced human umbilical vein relaxation

Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations

Impairments in microvascular function and skeletal muscle oxygenation in women with gestational diabetes mellitus: links to cardiovascular disease risk factors

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