Placenta 104 (2021) 71–80 Available online 27 November 2020 0143-4004/© 2020 Elsevier Ltd. All rights reserved. Decreased maternal serum adiponectin and increased insulin-like growth factor-1 levels along with increased placental glucose transporter-1 expression in gestational diabetes mellitus: Possible role in fetal overgrowth Manoharan Balachandiran a , Zachariah Bobby a, * , Gowri Dorairajan b , Victorraj Gladwin c , Vickneshwaran Vinayagam a , Rajaa Muthu Packirisamy a a Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India b Department of Obstetrics & Gynaecology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India c Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India A R T I C L E INFO Keywords: Gestational diabetes mellitus Insulin like growth factor-1 Adipokine Insulin/IGF-1 signalling Glucose transporter-1 Fetal overgrowth ABSTRACT Introduction: The placental glucose transporter – 1 (GLUT-1) is involved in the transplacental glucose transport to the fetus. GLUT-1 expressions are increased in diabetic pregnancies and associated with altered fetal growth. However, the factors regulating the GLUT-1 expressions are largely unknown. We hypothesised that maternal adipokines and insulin-like growth factor-1 (IGF1) modulate the placental expressions of GLUT-1 through the activation of insulin/IGF-1 signalling which may contribute to a fetal overgrowth in GDM. Methods: Maternal blood, cord blood and placental samples were collected from GDM and control pregnant women (CPW). The biochemical parameters, IGF1, adipokines, and high sensitive C- reactive protein were measured. We analysed the placental expressions of GLUT-1 and proteins related to insulin/IGF-1 signalling - insulin receptor –β, insulin receptor substrate – 1, phosphatidylinositol-3-kinase p110α, phospho Akt-1, phospho extracellular signal-regulated kinase 1/2, and nuclear factor-κB p65 in GDM and CPW. Results: Increased maternal IGF-1 and decreased adiponectin levels were found in the GDM women. Maternal IGF-1 levels were positively correlated, whereas adiponectin levels were negatively correlated with the birth weight of GDM newborns. Increased phosphorylation of Akt and ERK 1/2 was found in the placenta of GDM women. Placental expressions of GLUT-1 were signifcantly higher in the GDM women and positively correlated to the maternal IGF-1 levels in the GDM group. Discussion: Decreased maternal adiponectin and increased IGF-1 levels might have caused increased GLUT-1 expression via the increased activation of insulin/IGF-1 signalling in the placenta of GDM women which might have infuenced the fetal growth. 1. Introduction Fetal growth is mostly determined by nutrient supply, which is dependent upon the maternal nutritional status and placental nutrient transport. Studies reported that changes in placental nutrient transport cause altered fetal growth, such as intrauterine growth restriction (IUGR) or fetal overgrowth [1,2]. However, the factors regulating placental nutrient transport are not fully established in the pathology of pregnancy which results in altered fetal growth. Gestational diabetes mellitus (GDM) is defned as hyperglycemia frst developed or detected during gestation [3]. GDM is associated with fetal adiposity and overgrowth which causes adverse maternal and fetal outcomes. Further, it increases the risk of obesity, type 2 diabetes, and cardiovascular diseases in adult life [4]. High maternal blood glucose level is associated with an increase in birth weight of newborns in dia- betic mothers [5]. Maternal hyperglycemia contributes to fetal macro- somia by increasing substrate availability, stimulating excessive growth, and adiposity [6]. However, macrosomia is also observed even in newborns of diabetic mothers with satisfactory glycemic control [7,8]; this suggests that maternal factors other than nutrient levels could affect the nutrient supply to the growing fetus and causes fetal overgrowth. Glucose transporter-1 (GLUT-1) is the main glucose transporter in * Corresponding author. JIPMER, Puducherry, 605 006, India. E-mail address: zacbobby@yahoo.com (Z. Bobby). Contents lists available at ScienceDirect Placenta journal homepage: http://www.elsevier.com/locate/placenta https://doi.org/10.1016/j.placenta.2020.11.008 Received 4 September 2020; Received in revised form 2 November 2020; Accepted 24 November 2020