Placental expression of glucose transporters GLUT‐1, GLUT‐3, GLUT‐8 and GLUT‐12 in pregnancies complicated by gestational and type 1 diabetes mellitus

Abstract

Aims/Introduction: The aim of the present study was to evaluate the placental expression of glucose transporters GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in term pregnancies complicated by well-controlled gestational (GDM) and type 1 pregestational diabetes mellitus (PGDM). Materials and Methods: A total of 103 placental samples were obtained from patients diagnosed with GDM (n = 60), PGDM (n = 20) and a non-diabetic control group (n = 23). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected GLUT proteins. Results: Immunohistochemical techniques used for the identification of GLUT-1, GLUT-3, GLUT-8 and GLUT-12 revealed the presence of all glucose transporters in the placental tissue. Morphometric evaluation performed for the vascular density-matched placental samples demonstrated a significant increase in the expression of GLUT-1 protein in patients with PGDM as compared to GDM and control groups (P < 0.05). With regard to the expression of the other GLUT isoforms, no statistically significant differences were observed between patients from the diabetic and control populations. Positive correlations between fetal birthweight and the expression of GLUT-1 protein in the PGDM group (rho = 0.463, P < 0.05) and GLUT-12 in the control group (rho = 0.481, P < 0.05) were noted. Conclusions: In term pregnancies complicated by well-controlled GDM/PGDM, expression of transporters GLUT-3, GLUT-8 and GLUT-12 in the placenta remains unaffected. Increased expression of GLUT-1 among women with type 1 PGDM might contribute to a higher rate of macrosomic fetuses in this population.

Fetomaternal Expression of Glucose Transporters (GLUTs)—Biochemical, Cellular and Clinical Aspects

“…GLUT12 protein expression was mainly pronounced in the first trimester syncytial and extravillous trophoblast cells and term villous vascular smooth muscle cells, villous stromal cells and trophoblast cells of the chorion [ 80 , 81 ]. Further, Stanirowski et al confirmed GLUT8 and GLU12 protein expression in the term placental tissue by immunohistochemistry [ 82 , 83 ].…”

“…Both PGDM and GDM patients treated with insulin had significantly increased GLUT4 and GLUT9 protein expression compared to healthy controls [ 120 ]. Finally, there were no differences in the GLUT3, GLUT8, and GLUT12 protein expression in patients with PGDM and control pregnant women [ 82 ].…”

“…Thus, those differences in the GLUTs expression and increased glucose uptake may partially elucidate the pathogenesis of fetal overgrowth in patients with relatively well-controlled White class D diabetes, which is often associated with vascular abnormalities that could, rather, lead to fetal growth restriction [ 119 ]. Finally, the placental GLUTs (1, 4, and 9) protein expression was positively correlated with the fetal birth weight and neonatal subscapular and abdominal fat mass measurements [ 63 , 82 ].…”

“…Other studies found no differences in the placental GLUT4 or GLUT9 protein and mRNA expression between GDM and control pregnant women [ 47 , 75 , 78 , 91 ]. Further, there were no between-group differences in the GLUT8 and GLUT12 protein expression in patients with GDM and control pregnant women [ 82 ]. Zhang et al noted significantly decreased GLUT3 and GLUT4 expression in non-obese GDM pregnant patients compared with normal pregnant women [ 126 ].…”

Hyperglycemia in Pregnancy-Associated Oxidative Stress Augments Altered Placental Glucose Transporter 1 Trafficking via AMPKα/p38MAPK Signaling Cascade

“…Altered GLUT1 expression is discovered in pathological pregnancies, implicating abnormal glucose usage. Available documents suggest that GLUT1 was increased in HIP with or without a large infant [ 8 , 9 , 10 , 11 , 12 , 13 ]. In contrast, its expression is shown to be decreased in IUGR [ 14 ].…”