289 INSULIN INHIBITS THE SYNTHESIS OF THE MAJOR SURFACTANT APOPROTEIN IN HUMAN FETAL LUNG IN VITRO

Abstract

Fetal hyperinsulinemia may be a causative factor in the increased incidence of respiratory distress syndrome (RDS) in newborn infants of diabetic mothers. We previously observed, however, that insulin acted synergistically with cortisol to increase disaturated phosphatidylcholine synthesis in human fetal lung explants in vitro. Surfactant apoproteins, which comprise ∼10% of surfactant composition, may serve an important role in surfactant function. In the present study, we utilized antibodies directed against the major human surfactant apoprotein, a 35 kDa glycoprotein, and immunoblot analysis to evaluate the effect of insulin on the specific content of this protein in human fetal lung explants in organ culture. The 35 kDa protein, which was not observed in the human fetal lung tissue prior to culture, was detectable in control explants after 2 days of incubation and was increased in concentration with increasing time in culture. Insulin caused a marked inhibition of surfactant apoprotein accumulation at concentrations as low as 0.5 nM. This inhibitory effect of insulin was dose-dependent and was apparent as early as day 2 of incubation. These findings are suggestive that fetal hyperinsulinemia may cause the production of surfactant deficient in the major apoprotein; this may provide an explanation for the increased incidence of RDS in infants of diabetic mothers.