Expression and correlation of sex hormone-binding globulin and insulin signal transduction and glucose transporter proteins in gestational diabetes mellitus placental tissue

Abstract

Objective: The aim of the present study was to investigate the probable pathogenesis of gestational diabetes mellitus (GDM) by analyzing the correlation between sex hormone-binding globulin (SHBG) secreted by the placenta during pregnancy and insulin signaling components and glucose transporter proteins (GLUTs) in the placental tissue.

Design and methods: Placental tissue was collected from full-term and non-obese [body mass index <25kg/m(2)] pregnant women; 10 diagnosed with GDM and 10 with normal pregnancy. We used real-time polymerase chain reaction (PCR), immunohistochemistry and western blotting to detect expression of protein and mRNA of SHBG and insulin signaling components and GLUTs in placental tissue.

Results: In the placental tissue of non-obese women, there was a decrease in expression of SHBG protein and mRNA, with a concurrent decrease in expression of GLUT-4 protein and mRNA in women with GDM compared with normal controls. There was a decrease in GLUT-3 and insulin receptor substrate (IRS)-1 protein expression and lower IRS-2 mRNA expression was also observed in GDM placental tissue. Linear correlation analyses showed a positive correlation between SHBG and IRS-2 mRNA (P=0.038, R(2)=0.2178, y=0.249x+1.4208); positive correlation between SHBG and phosphatidylinositol 3-kinase (PI3K) p85α mRNA (P=0.035, R(2)=0.224, y=0.3506x+0.7433); positive correlation between SHBG and GLUT-4 mRNA (P=0.000, R(2)=0.5174, y=1.3822+1.7811x); positive correlation between IRS-2 and GLUT-4 mRNA (P=0.002, R(2)=0.4064, y=-0.8272+2.9592x); negative correlation between IRS-1 and PI3K p85α mRNA (P=0.005, R(2)=0.366, y=2.4492-0.1929x); negative correlation between IRS-1 and GLUT-3 mRNA (P=0.027, R(2)=0.243, y=0.9254-0.0714x); and positive correlation between IRS-2 and GLUT-1 mRNA (P=0.004, R(2)=0.3794, y=0.0225+0.6298x).

Conclusion: The results confirm that defective receptors for insulin signal transduction and GLUT proteins are present in GDM placental tissue. Decreasing expression of SHBG may participate in regulation of insulin signaling, leading to a concomitant decrease in expression of relevant insulin signaling components in placental tissue, implying insulin resistance and eventual development of GDM.

Keywords: Gestational diabetes mellitus; Glucose transport protein; Insulin receptor substrate; Phosphatidylinositol 3-kinase; Sex hormone-binding globulin.