Does hyperoxia affect glucose regulation and transport in the newborn?

Objective: Hyperglycemia has been found to occur in children placed on cardiopulmonary bypass. Our laboratory demonstrated that hyperoxia plays a role in this hyperglycemic response and also occurs in the absence of cardiopulmonary bypass. The purpose of this study was to elucidate potential mechanisms underlying the hyperoxic-induced hyperglycemia by examining glucagon, insulin, and epinephrine, which are important in glucose regulation and skeletal and cardiac glucose transporters (GLUT1 and GLUT4), which facilitate glucose entry. Methods: Three-day-old piglets were anesthetized, intubated, and ventilated to normoxia. Animals were then randomly allocated to either 5 hours of normoxia (n = 4) or hyperoxia (n = 6). Measurements of oxygen, blood glucose, plasma glucagon, insulin, and epinephrine levels were made. Total GLUT1 and GLUT4 content in cardiac and skeletal muscle was measured using Western blotting analysis. Results: A sustained hyperglycemic response (P <.001) was seen throughout the 5-hour ventilatory period. A significant twofold elevation in glucagon levels (P <.001) and a threefold elevation (P <.003) in plasma insulin levels occurred, despite no significant changes in plasma epinephrine. Total GLUT1 and GLUT4 content were significantly reduced in skeletal muscle by 66% and 59%, respectively, while no significant changes occurred in cardiac muscle. Conclusion: This study demonstrates that significant elevations in glucagon and insulin and reductions in total skeletal muscle GLUT1 and GLUT4 content all contribute to hyperoxia-induced hyperglycemia seen in newborns. To optimize postoperative recovery of newborns, consideration should be given to the levels of oxygen used to avoid the potential development of insulin resistance and subsequent decrease in glucose entry.