Effects of insulin and glucose on pulmonary insulin receptors in late gestation fetal rats

The effects of high glucose and insulin concentrations on fetal lung insulin receptors and tyrosine kinase activity were studied in an in vitro system utilizing 19- or 20-d fetal rat lung explants. Exposure of the explants to 100 mM glucose and insulin (0.1 unit/mL) for 72 h resulted in a significant decrease in specific binding of insulin to partially purified receptors [5.78% ± 0.66 (SEM) vs. 9.64% ± 1.68; P <.01] when compared with lung explants exposed to 10 mM glucose alone. When individual effects of high insulin and glucose were studied, down-regulation of specific insulin binding was also observed, but to a lesser extent than that observed using both high glucose and insulin. Differences in insulin receptor affinity were not noted. Insulin receptor tyrosine kinase activity was also significantly decreased (52% of control values) under high-glucose/high-insulin conditions. Total phosphatidylcholine and disaturated phosphatidylcholine concentrations were significantly decreased in explants grown under high-glucose/high-insulin conditions, consistent with delayed pulmonary maturation. High glucose and insulin levels thus result in down-regulation of fetal lung insulin receptors and insulin receptor tyrosine kinase activity late in gestation. These results may have implications for substrate availability in the developing fetal lung.