Effect of maternal diabetes upon fetal rat myocardial and skeletal muscle glucose transporters.

Abstract

We investigated the effect of streptozotocin-induced short-term maternal diabetes upon fetal rat myocardial and skeletal muscle glucose transporter Glut 1 (basal form) and Glut 4 (insulin-responsive form) protein concentrations by Western blot analysis. In the severely diabetic group (SEVERE-D, n = 17), a 3-fold increase in maternal and fetal glucose concentrations (p < 0.01) was associated with a 3-fold decline in maternal (p < 0.01) with no change in fetal insulin levels when compared with the streptozotocin-treated nondiabetic (n = 10) and vehicle-treated control (control, n = 14) groups. These changes in the SEVERE-D group when compared with controls were associated with a 30 and 65% decline, respectively, in fetal myocardial and skeletal muscle (forelimb and hind limb) Glut 1 protein concentrations. The fetal myocardium also demonstrated a 45% decline in Glut 4 protein levels. Fetal skeletal muscle Glut 4 protein, which was expressed only at very low levels in controls showed no change in SEVERE-D. Immunohistochemical analysis revealed a myocyte-plasma membrane association of Glut 1 and an intracellular Glut 4 distribution in the fetal myocardium and skeletal muscle. No Glut 1 immunoreactivity was noted in either the fetal myocardial or skeletal muscle perineural sheaths, blood vessels, or the entrapped fetal red blood cells. This subcellular localization pattern was unaltered in all three treatment groups. We conclude that maternal diabetes causing fetal hyperglycemia with normoinsulinemia suppresses fetal myocardial Glut 1 and Glut 4 and fetal skeletal muscle Glut 1. The decline in the plasma membrane associated Glut 1 concentrations may serve a protective function by reducing the glucose transport rate into fetal myocardial and skeletal muscle cells, which otherwise could be vulnerable to high circulating glucose. The in-utero maternal diabetes induced decrease in fetal myocardial intracellular-Glut 4 concentration could herald the emergence of insulin resistance.