Role of Insulin in Placental Transport of Nutrients in Gestational Diabetes Mellitus

Abstract

Background: Gestational diabetes mellitus (GDM) is associated with increased fetal adiposity, which may increase the risk of obesity in adulthood. The placenta has insulin receptors and maternal insulin can activate its signaling pathways, affecting the transport of nutrients to the fetus. However, the effects of diet or insulin treatment on the placental pathophysiology of GDM are unknown. Summary: There are very few studies on possible defects in the insulin signaling pathway in the GDM placenta. Such defects could influence the placental transport of nutrients to the fetus. In this review we discuss the state of insulin signaling pathways in placentas of women with GDM, as well as the role of exogenous insulin in placental nutrient transport to the fetus, and fetal adiposity. Key Messages: Maternal insulin in the third trimester is correlated with fetal abdominal circumference at that time, suggesting the important role of insulin in this process. Since treatment with insulin at the end of pregnancy may activate placental nutrient transport to the fetus and promote placental fatty acid transfer, it would be interesting to improve maternal hyperlipidemia control in GDM subjects treated with this hormone. More research in this area with high number of subjects is necessary.

The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology <em>In Vivo</em>

“…However, the effect of insulin via the insulin signaling pathway might be important for placental growth, the placental nutrient sensing system and the regulation and abundance of nutrient transporters in the syncytiotrophoblast (57). We found no correlation between maternal insulin and placental weight, in contrast to results earlier published by this group (157).…”

“…This explains why a rapid effect of insulin on the placental glucose transport cannot be demonstrated, and GLUT4 is not considered to be important for the maternalfetal transfer (56). However, insulin receptors are present in the syncytiotrophoblast and complete syncytial insensitivity to glucose cannot be assumed (57).…”

“…The authors speculate that the increased fetal glucose consumption contributes to maternal euglycamia later in pregnancy(64). The direct effect of insulin treatment on the development of the conceptus, beyond reduction of malformations, is largely unknown(57,58,99,106).Altogether, the mechanisms linking maternal glucose levels and fetal growth are not fully understood and still a subject of interest for researchers.Maternal mal-or undernutrition is associated with IUGR and alteredplacental size and function. In developed countries IUGR is believed to be predominately caused by primary placental insufficiency and/or reduced perfusion of the placenta in the absence of maternal malnutrition, both of which may cause reduced maternal supply of nutrient to the placenta.Experimental fetal IUGR caused by undernutrition, hypothermia, reduced placental flow by uterine ligation and fetal hypoglycemia are perhaps the perturbations best studied in relation to placental transfer and metabolism in a variety of animal models (5, 7, 118).…”

Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism

“…Also, they reported increased placental nutrient transport to the fetus and the enhanced placental fatty acid transfer may favour fetal adiposity [38]. However, this activation is also mediated by inflammatory cytokines, hormones and growth factors [39].…”

Molecular pathways disrupted by gestational diabetes mellitus

“…The binding of insulin to insulin receptor activates the autophosphorylation on specific cytoplasmic tyrosine residues, which ensues downstream signalling (Pessin & Saltiel 2000). Although the insulin receptor is not implicated in placental glucose transport, placental insulin signalling may instead contribute to lipid metabolism (Ruiz-Palacios et al 2017). Examination of GDM placenta displayed reduced expression of insulin receptor together with reduced phosphorylation of its downstream molecule, Akt (Li et al 2016).…”