Increased IRS2 mRNA Expression in SGA Neonates: PCR Analysis of Insulin/IGF Signaling in Cord Blood

CONTEXT: Hypoglycemia is the most common metabolic problem among small-for-gestational-age (SGA) neonates. However, the pathological mechanism and insulin/ insulin-like growth factor (IGF) signaling axis in neonates remain unknown. OBJECTIVE: To determine the insulin/IGF axis in neonates, we analyzed the messenger RNA (mRNA) expression of insulin/IGF signaling in fetal umbilical cord blood. SETTING: The Perinatal Medical Center of Tottori University Hospital. PARTICIPANTS: Fifty-two [42 appropriate-for-gestational-age (AGA) and 10 SGA] neonates. INTERVENTIONS: Immediately collected cord blood was placed into a PAXgene Blood RNA Tube. Total RNA from the blood was purified using reagents provided in the PAXgene Blood RNA Kit within 4 days, and reverse transcription polymerase chain reaction (PCR) was performed. MAIN OUTCOME MEASURE: Quantitative real-time PCR analysis was applied to evaluate the mRNA expression of insulin receptor (INSR), IGF-I receptor (IGF1R), insulin receptor substrate 1 (IRS1), IRS2, and glucose transporters (SLC2A2 and SLC2A4). β-Actin was used as a control gene. RESULTS: Serum glucose and IGF-I levels in SGA neonates were significantly lower. The cord serum insulin levels were similar between AGA and SGA neonates. The IRS2 mRNA expression was significantly higher in SGA than in AGA neonates (P < 0.05). The IRS2 mRNA expression was significantly higher in hypoglycemic SGA neonates than in normoglycemic SGA neonates. CONCLUSIONS: We determined that intrauterine growth restriction induces increased IRS2 mRNA expression in cord blood, without hyperinsulinemia. The increased expression of IRS2 mRNA might be associated with abnormal glucose metabolism in SGA neonates. Our findings might lead to the elucidation of abnormal glucose metabolism in SGA neonates.