Effects of selective hyperglycemia and hyperinsulinemia on glucose transporters in fetal ovine skeletal muscle

Abstract

We measured net fetal glucose uptake rate from the placenta, shown previously to be equal to total fetal glucose utilization rate (GURf) and proportional to fetal hindlimb skeletal muscle glucose utilization, under normal conditions and after 1, 2.5, and 24 h of selective hyperglycemia (↑G) or selective hyperinsulinemia (↑I). We simultaneously measured the amount of Glut 1 and Glut 4 glucose transporter proteins in fetal sheep skeletal muscle. With ↑G, GURf was increased ∼40% at 1 and 2.5 h but returned to the control rate by 24 h. This transient ↑G-specific ↑GURf was associated with increased plasma membrane-associated Glut 1 (4-fold) and intracellular Glut 4 (3-fold) protein beginning at 1 h. With ↑I, GURf was increased ∼70% at 1, 2.5, and 24 h. This more sustained ↑I-specific ↑GURf was associated with a significant increase in Glut 4 protein (2-fold) at 2.5 h but no change in Glut 1 protein. These results show that ↑G and ↑I have independent effects on the amount of Glut 1 and Glut 4 glucose transporter proteins in ovine fetal skeletal muscle. These effects are time dependent and isoform specific and may contribute to increased glucose utilization in fetal skeletal muscle. The lack of a sustained temporal correlation between the increase in transporter proteins and glucose utilization rates indicates that subcellular localization and activity of a transporter or tissues other than the skeletal muscle contribute to net GURf.