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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1866

Review

Subiabre, Mario¹  Villalobos-Labra, Roberto¹  Silva, Luis^1,2  Fuentes, Gonzalo^1,3  Toledo, Fernando^1,4  Sobrevia, Luis^1,5,6 

[1] Pontificia Univ Catolica Chile, Fac Med, Div Obstet & Gynaecol, Dept Obstet,CMPL,Sch Med, Santiago 8330024, Chile

[2] Univ Groningen, Immunoendocrinol, Dept Pathol & Med Biol, Div Med Biol,UMCG, NL-9700 RB Groningen, Netherlands

[3] Univ Antofagasta, Fac Hlth Sci, Biomed Dept, Cell Physiol Lab, Antofagasta 1270300, Chile

[4] Univ Bio Bio, Fac Sci, Dept Basic Sci, Chillan 3780000, Chile

[5] Univ Seville, Fac Pharm, Dept Physiol, E-41012 Seville, Spain

[6] Univ Queensland, UQCCR, Fac Med & Biomed Sci, Herston, Qld 4029, Australia

关键词: Diabetes;    Endothelium;    Membrane transport;    Receptor;    Insulin;    Adenosine;    Adipokines;   

DOI  :  10.1016/j.bbadis.2018.12.021

来源: Elsevier

【 摘 要 】

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 A2A 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.

【 授权许可】

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