Functional Link Between Adenosine and Insulin: A Hypothesis for Fetoplacental Vascular Endothelial Dysfunction in Gestational Diabetes

Enrique      Guzman-Gutierrez; Fernando      Abarzua; Cristian      Belmar; Jyh      K. Nien; Marco      A. Ramirez; Pablo      Arroyo; Carlos      Salomon; Francisco      Westermeier; Carlos      Puebla; Andrea      Leiva; Paola      Casanello; Luis      Sobrevia

doi:10.2174/157016111797484062

Abstract

Gestational diabetes mellitus (GDM) is a syndrome compromising the health of the mother and the fetus. Endothelial damage and reduced metabolism of the vasodilator adenosine occur and fetal hyperinsulinemia associated with deficient insulin response and a metabolic rather than mitogenic phenotype is characteristic of this pathology. These phenomena lead to endothelial dysfunction of the fetoplacental unit. Major databases were searched for the relevant literature in the field. Special attention was placed on publications related with diabetes and hormone/metabolic disorders. We aimed to summarize the information regarding insulin sensitivity changes in GDM and the role of adenosine in this phenomenon. Evidence supporting the possibility that fetal endothelial dysfunction involves a functional link between adenosine and insulin signaling in the fetal endothelium from GDM pregnancies is summarized. Since insulin acts via membrane receptors type A (preferentially associated with mitogenic responses) or type B (preferentially associated with metabolic responses), a differential activation of these receptors in this syndrome is proposed.

Keywords: Adenosine, endothelium, fetus, gestational diabetes, insulin receptor, placenta, hyperinsulinemia, endothelial dysfunction, oral glucose tolerance test, macrosomia