title: High glucose causes delayed fetal lung maturation in vitro.
abstract: The diabetic pregnancy is characterized by a delay in the process of fetal lung maturation. To determine whether high glucose conditions per se have an adverse impact on fetal lung phospholipid metabolism, 20-day fetal rat lung explants were cultured in F-12 medium (10 mM glucose) to which glucose was added to achieve final concentrations of 10, 25, 50, and 100 mM. Significant dose-dependent decreases in the rate of incorporation of [H3]choline into PC were noted at high glucose concentrations: Rate of choline incorporation was decreased by 19 and 28% under 50 and 100 mM glucose conditions, respectively (p < .001). Similar results were obtained when choline incorporation into DSPC was assayed. Equiosmolar mannitol concentrations did not result in comparable decreases, indicating a specific adverse effect attributable to glucose. Total PC and DSPC contents were also decreased by approximately 25% under high glucose conditions (p < .001). Glycogen concentrations were increased two- to threefold in the explants grown under high glucose conditions, consistent with a less mature lung. The addition of 1 unit/mL of insulin to F-12 medium did not result in decreases in choline incorporation into PC or DSPC; the addition of this amount of insulin to medium containing 100 mM glucose did not result in further decreases in choline incorporation rate. These results indicate that high glucose alone can have an adverse effect on fetal lung maturation in vitro and may be involved in the pathogenesis of the delay in fetal lung development observed in the diabetic pregnancy.
authors.affiliation: Division of Neonatology, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: I H
authors.initials: IH
authors.lastname: Gewolb
mesh_terms: D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000196:embryology* / Q000378:metabolism*; D009994:Osmolar Concentration; D010713:Phosphatidylcholines / Q000037:antagonists & inhibitors / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D007328:Insulin; D010713:Phosphatidylcholines; C017463:lecithins, disaturated; D007770:L-Lactate Dehydrogenase; D005947:Glucose