title: Effects of insulin and glucose on pulmonary insulin receptors in late gestation fetal rats.
abstract: 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 less than .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.
authors.affiliation: Division of Neonatology, University of Rochester Medical Center, New York.
authors.forename: E
authors.initials: E
authors.lastname: Zmora
authors.forename: I H
authors.initials: IH
authors.lastname: Gewolb
authors.forename: D L
authors.initials: DL
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D009994:Osmolar Concentration; D010743:Phospholipids / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*
chemical_list: D007328:Insulin; D010743:Phospholipids; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose