Role of insulin, adenosine, and adipokine receptors in the foetoplacental vascular dysfunction in gestational diabetes mellitus.

Mario Subiabre, Roberto Villalobos-Labra, Luis Silva, Gonzalo Fuentes, Fernando Toledo, Luis Sobrevia

Journal: Biochimica et biophysica acta. Molecular basis of disease 2020;1866(2):165370

PMID: 30660686

Free Full Text on Elsevier Science View on PubMed

Abstract

Gestational diabetes mellitus (GDM) is a disease of pregnancy associated with maternal and foetal hyperglycaemia and altered foetoplacental vascular function. Human foetoplacental microvascular and macrovascular endothelium from GDM pregnancy show increased maximal l-arginine transport capacity via the human cationic amino acid transporter 1 (hCAT-1) isoform and nitric oxide (NO) synthesis by the endothelial NO synthase (eNOS). These alterations are paralleled by lower maximal transport activity of the endogenous nucleoside adenosine via the human equilibrative nucleoside transporter 1 (hENT1) and activation of adenosine receptors. A causal relationship has been described for adenosine-activation of A adenosine receptors, hCAT-1, and eNOS activity (i.e. the Adenosine/l-Arginine/Nitric Oxide, ALANO, signalling pathway). Insulin restores these alterations in GDM via activation of insulin receptor A (IR-A) form in the macrovascular but IR-A and IR-B forms in the microcirculation of the human placenta. Adipokines are secreted from adipocytes influencing the foetoplacental metabolic and vascular function. Various adipokines are dysregulated in GDM, with adiponectin and leptin playing major roles. Abnormal plasma concentration of these adipokines and the activation or their receptors are involved in the pathophysiology of GDM. However, involvement of adipokines, adenosine, and insulin receptors and membrane transporters in the aetiology of this disease of pregnancy is unknown. This review focuses on the pathophysiology of insulin and adenosine receptors and l-arginine and adenosine membranes transporters giving an overview of the key adipokines leptin and adiponectin in the foetoplacental vasculature in GDM. This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.

Address: Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile. Electronic address: [email protected].; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen (UMCG), Groningen 9700 RB, the Netherlands.; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Cell Physiology Laboratory, Biomedical Department, Faculty of Health Sciences, Universidad de Antofagasta, Antofagasta 1270300, Chile.; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Department of Basic Sciences, Faculty of Sciences, Universidad del Bío Bío, Chillán 3780000, Chile.; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-41012, Spain; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston 4029, Queensland, Australia. Electronic address: [email protected].

DOI: 10.1016/j.bbadis.2018.12.021

Link outs

Free resources

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0925...

Medical:

https://medlineplus.gov/diabetesmedicines.html

Miscellaneous:

https://assays.cancer.gov/CPTAC-1771

MeSH Terms: Adenosine, Adipokines, Antigens, CD, Arginine, Biological Transport, Cationic Amino Acid Transporter 1, Diabetes, Gestational, Endothelium, Endothelium, Vascular, Equilibrative Nucleoside Transporter 1, Female, GTPase-Activating Proteins, Humans, Insulin, Nitric Oxide, Nitric Oxide Synthase Type III, Placenta, Pregnancy, Protein Isoforms, Receptor, Insulin, Receptors, Adipokine, Receptors, Purinergic P1, Signal Transduction