1. Background Hyperglycemia has been reported in up to 80% of ELBW infants and is associated with increased morbidity and mortality. 1-3 Glucose instability is common in newborns; however, postnatal glucose regulation is understudied and the developmental mechanisms of glucose remain fragmentary. Baboons are relevant non-human primate models as they have close phylogenetic proximity to humans. In addition, premature baboons develop hyperglycemia after birth making them an excellent model to study hepatic gluconeogenesis and to examine the underlying processes responsible for aberrant glucose regulation in the perinatal period. 4 Glucose Metabolism in Prematurity: Evidence of Hepatic Insulin Resistance and Molecular Developmental Differences in Non-Human Primates Lisa McGill-Vargas PGY5, Marney Johnson, Steve Seidner, Don McCurnin, Teresa Johnson-Pais, Ralph DeFronzo and Cynthia L Blanco University of Texas Health Science Center at San Antonio Results Hypotheses Preterm baboons have an impaired ability to suppress endogenous glucose production (EGP) during hyperinsulinemia when compared to term baboons. Developmental differences exist in the fetal hepatic gluconeogenic pathway. Materials & Methods Fetal group: eighteen fetal baboons were delivered at 125 day (d) gestational age (GA), 140d GA and 175d GA (term=185d GA) via C- section and sacrificed right after birth. Postnatal group: fifteen baboons were delivered at 125d GA or at term; preterm animals were sedated, intubated and chronically ventilated. Postnatal group: a hyperinsulinemic euglycemic clamp to quantify EGP was performed at day of life 5 and 14. Serum insulin and epinephrine concentrations were measured at baseline (B) and under insulin stimulation (I). Fetal & Postnatal groups: Protein content and gene expression of key gluconeogenic/insulin signaling molecules were measured: Phosphoenolpyruvate carboxykinase (PEPCK) Glucose-6-phosphatase (G6Pase) Transcription factor forkhead box-01 (FoxO1) ANOVA and T-tests with SPSS 17.0. Future Directions To correlate developmental differences in gluconeogenic molecules with glucose control in the perinatal period To study additional transcription factors interplaying in gene expression of key gluconeogenic enzymes References 1.Beardsall et al. Prevalence and Determinants of Hyperglycemia in Very Low Birth Weight Infants: Cohort Analyses of the NITURE Study. The Journal of Pediatrics 2010 Nov; 157(5):715-9. 2.Blanco et al. Hyperglycemia in Extremely Low Birth Weight Infants in a Predominantly Hispanic Population and Related Morbidities. Journal of Perinatology 2006 Dec;26(12):737-741. 3.Garg et al. Hyperglycemia and Retinopathy of Prematurity in Very Low Birth Weight Infants. Journal of Perinatology 2003 Apr;23(3):186-94. 4.McGill-Vargas et al. Hyperglycemia Increases the Risk of Death in Extremely Preterm Baboons. Pediatr Res 2013 Mar;73(3):337-43. Texas Pediatric Society Electronic Poster Contest Results Conclusions Preterm postnatal baboons have persistent EGP after maximal insulin stimulation, placing them at an increased risk for hyperglycemia. Fetal PEPCK protein and gene expression increases with advancing gestational age. Postnatally, PEPCK gene expression increases with maturation into adulthood. Fetal G6Pase decreases transiently in late gestation. After birth, G6Pase is higher in preterm animals when compared to their term and adult counterparts. These changes may contribute to aberrant glucose control in the perinatal period.