HIGH GLUCOSE AND INSULIN DECREASE FETAL LUNG INSULIN-RECEPTOR MESSENGER-RNA AND TYROSINE KINASE-ACTIVITY IN-VITRO

Specific insulin binding by the fetal lung insulin receptor is reduced in vitro by a combination of high glucose and insulin. Using 19-22 da y fetal rat lung, we studied the effect of culture for 48 hours under conditions of low (10mM) and high (100mM) glucose with and without add ed insulin on insulin receptor tyrosine kinase activity, mRNA abundanc e, and glucose uptake. Culture in high glucose + insulin reduced tyros ine kinase activity to 77.2 +/- 5.2% of control values (p <.001); high glucose or insulin alone had no effect. Insulin-receptor mRNA abundan ce was reduced by high glucose + insulin to 37 +/- 6% of control value s (p <.05). Again, no significant differences were seen with high gluc ose or insulin alone. Uptake of H-3-2-deoxy-glucose by explants cultur ed under high glucose + insulin conditions was also significantly redu ced. These data indicate that down-regulation of fetal lung insulin re ceptors by high glucose + insulin occurs at the pre-translational leve l and that glucose transport is adversely affected under these conditi ons. Down-regulation of lung insulin receptors late in fetal life may limit the availability of glucose as substrate for surfactant synthesi s in the perinatal period and may partially explain the increased inci dence of respiratory (C) 1994 Academic Press, Inc.