Abstract 285 Neonatal Nutrition and Metabolism I Poster Symposium, Saturday, 5/1

Glucose, an essential substrate for cellular oxidative metabolism, is transported in various tissues by a family of facilitative glucose transporter proteins. We have previously demonstrated the chronic effect of fetal hyperglycemia with/without hyperinsulinemia upon fetal tissue (brain, liver, heart, skeletal muscle & fat) glucose transporter isoforms ( Am. J. Physiol. 1999 in press). In the present study we investigated the acute effect (30 min to 24 hr) of selective hyperglycemia or hyperinsulinemia upon fetal tissue glucose transporter isoforms. We accomplished selective hyperglycemia with normoinsulinemia (HG) by infusing glucose into the mother and somatostatin into the fetus of a chronically catherized pregnant sheep model (n=11), while selective hyperinsulinemia with euglycemia (HI) was accomplished by fetal insulin infusion with a glucose clamp (n=10). The control group (C) consisted of gestational age matched, euglycemic and normoinsulinemic animals (n=5). Fetal brain (Glut 1 and Glut 3), liver (Glut 1), skeletal muscle, fat, and myocardium (Glut 1 and Glut 4) glucose transporter proteins were assessed by Western blot analysis using isoform specific antibodies. While no effect of HG or HI was observed on fetal brain Glut 1 (50 kD) or Glut 3 (50 kD) levels, and no effect of HI was noted on liver Glut 1 (50 kD), HG led to a 50% decline in liver Glut 1 levels (p<0.05) when compared to C. In the classically insulin-responsive tissues, while HG led to no change in skeletal muscle and fat Glut 1 (50 kD) or Glut 4 (45 kD) levels, a 40% decline was noted in myocardial Glut 4 (p<0.05) alone. HI caused no change in skeletal muscle and fat Glut 1 but a 2-fold increase in skeletal muscle Glut 4 alone (p<0.05). In contrast, HI caused no change in myocardial Glut 1 or Glut 4 levels. We conclude that 1] fetal tissue glucose transporters are regulated independently by acute perturbations in circulating glucose and insulin concentrations in a tissue- and isoform- specific manner, 2] brain glucose transporter isoforms (Glut 1 or Glut 3) are not amenable to acute perturbations, 3] HG caused a tissue-specific differential response leading to a decline in hepatic Glut 1, and a decline in myocardial Glut 4. 4] In contrast, HI while not affecting the other tissue (liver, myocardium, fat) glucose transporter isoforms (Glut 1 and Glut 4), led to an increase in skeletal muscle Glut 4 alone. We speculate that the differential effects of selective HG and HI upon fetal tissue glucose transporters may play additive roles in clinical situations associated with hyperglycemia and hyperinsulinemia.

[Supported by NIH-HD33997, HD25024, HD28794, & HD20761]