Real Time RT-PCR Analysis of Glucose Utilization Enzymes in Skeletal Muscle of Preterm vs. Full Term Neonates

Abstract

Preterm birth is a serious and costly health problem, which affects nearly 1 in 8 births in the United States. Intravenous, or parenteral, nutrition is often required in very preterm infants (<33 weeks gestational age), whose digestive tracts are too immature to receive enteral nutrition. Unfortunately, current parenteral feeding methods are also associated with metabolic complications including hyperglycemia, which is a primary factor in postnatal morbidity and mortality. Peripheral insulin resistance is a key factor contributing to hyperglycemia in preterm neonates receiving parenteral nutrition, but the relationship between preterm birth and mechanisms of insulin-stimulated glucose disposal are not well understood. We hypothesized that compared to neonates born full term, preterm neonates possess a diminished capacity for glucose uptake and usage in skeletal muscle. To test this, mRNA transcript amounts were measured in skeletal muscle tissue of preterm and term pigs (delivered on days 106 and 114 of gestation, respectively). Tissue was collected after 6 d of parenteral feeding and transcript amounts for enzymes involved in glucose transport (GLUT1 and GLUT4), glycogen synthesis (glycogen synthase), glycogen degradation (glycogen phosphorylase), and fatty acid oxidation (carnitine palmitoyltransferase I [CPT I]) were determined. Preterm pigs displayed increased (P < 0.05) expression of GLUT4, CPT I, and glycogen phosphorylase transcripts relative to term pigs. This suggests that mechanisms for glucose uptake in the preterm neonate are immaturely developed and that muscle cells derive energy more heavily from fatty acids and glycogen stored prenatally as alternatives to circulating glucose. Further investigation of the activity and protein quantities of these enzymes is necessary to validate these conclusions.