ArticleDiabetes2011
Insulin restores gestational diabetes mellitus-reduced adenosine transport involving differential expression of insulin receptor isoforms in human umbilical vein endothelium.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 111 citations in OpenAlex.
- A conceptual review of intracellular pH as a regulator of the adenosine-L-arginine-nitric oxide (ALANO) axis in human fetoplacental endothelial dysfunction in gestational diabetes mellitus.Pflugers Archiv : European journal of physiology · 2026Review
- Article
- Flickering of fetal erythrocytes membrane under gestational diabetes observed with dual time resolved membrane fluctuation spectroscopy.Biochemistry and biophysics reports · 2023Article
- The Regulation of Endothelin-1 in Pregnancies Complicated by Gestational Diabetes: Uncovering the Vascular Effects of Insulin.Biomedicines · 2023Article
- Proteomics and bioinformatics analysis of cardiovascular related proteins in offspring exposed to gestational diabetes mellitus.Frontiers in cardiovascular medicine · 2022Article
- Endothelial Dysfunction in Pregnancy Complications.Biomedicines · 2021Review
- Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta.Frontiers in endocrinology · 2021Article
- Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes.Frontiers in physiology · 2021Review
- Article
- O-GlcNAc impairs endothelial function in uterine arteries from virgin but not pregnant rats: The role of GSK3β.European journal of pharmacology · 2020Article
- Article
- Transcriptional Regulation ofGenes · 2019Review
- Maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature.Scientific reports · 2018Article
- Who Is Who in Adenosine Transport.Frontiers in pharmacology · 2018Review
- High plasma adenosine levels in overweight/obese pregnant women.Purinergic signalling · 2017Article
- Insulin Receptor Isoforms in Physiology and Disease: An Updated View.Endocrine reviews · 2017Review
- Deficient Insulin-mediated Upregulation of the Equilibrative Nucleoside Transporter 2 Contributes to Chronically Increased Adenosine in Diabetic Glomerulopathy.Scientific reports · 2017Article
- Maternal low thyroxin levels are associated with adverse pregnancy outcomes in a Chinese population.PloS one · 2017Article
- Pro-angiogenic Role of Insulin: From Physiology to Pathology.Frontiers in physiology · 2017Review
- Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy.Journal of diabetes research · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo determine whether insulin reverses gestational diabetes mellitus (GDM)-reduced expression and activity of human equilibrative nucleoside transporters 1 (hENT1) in human umbilical vein endothelium cells (HUVECs). RESEARCH DESIGN AND
methodsPrimary cultured HUVECs from full-term normal (n = 44) and diet-treated GDM (n = 44) pregnancies were used. Insulin effect was assayed on hENT1 expression (protein, mRNA, SLC29A1 promoter activity) and activity (initial rates of adenosine transport) as well as endothelial nitric oxide (NO) synthase activity (serine(1177) phosphorylation, l-citrulline formation). Adenosine concentration in culture medium and umbilical vein blood (high-performance liquid chromatography) as well as insulin receptor A and B expression (quantitative PCR) were determined. Reactivity of umbilical vein rings to adenosine and insulin was assayed by wire myography. Experiments were in the absence or presence of l-N(G)-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) or ZM-241385 (an A(2A)-adenosine receptor antagonist).
resultsUmbilical vein blood adenosine concentration was higher, and the adenosine- and insulin-induced NO/endothelium-dependent umbilical vein relaxation was lower in GDM. Cells from GDM exhibited increased insulin receptor A isoform expression in addition to the reported NO-dependent inhibition of hENT1-adenosine transport and SLC29A1 reporter repression, and increased extracellular concentration of adenosine and NO synthase activity. Insulin reversed all these parameters to values in normal pregnancies, an effect blocked by ZM-241385 and l-NAME.
conclusionsGDM and normal pregnancy HUVEC phenotypes are differentially responsive to insulin, a phenomenon where insulin acts as protecting factor for endothelial dysfunction characteristic of this syndrome. Abnormal adenosine plasma levels, and potentially A(2A)-adenosine receptors and insulin receptor A, will play crucial roles in this phenomenon in GDM.
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