Chronic glucose infusion inhibits development of beta-receptor binding in fetal lamb lung.
We used chronic fetal glucose infusion to test the hypothesis that chronic fetal hyperglycemia and hyperinsulinemia inhibit the development of beta-receptor binding capacity (Bmax) in fetal lamb lung. Glucose was infused (14 +/- 4 mg/kg/h, mean +/- SD) into eight twin and four singleton fetuses from 112 days gestation until death between 118-145 days gestation. The other eight twins and eleven additional singleton fetuses served as controls. Serum glucose levels were elevated 2-fold and serum insulin levels were elevated 3-fold in the glucose-infused fetuses. In the control fetuses beta-receptor Bmax increased 2.5-fold between 130 days gestation and term. However, this increase was attenuated to 1.5-fold in the glucose infused fetuses, p less than 0.01. The 50% inhibition of Bmax was similar in both male and female fetuses, except that the Bmax fell to 30% lower levels in males, p less than 0.01. Chronic glucose infusion also resulted in an 80% reduction in lung lavage saturated phosphatidylcholine content, and an 85% reduction in tracheal fluid saturated phosphatidylcholine content, p less than 0.001. Lung lavage and tracheal fluid saturated phosphatidylcholine content correlated significantly with beta receptor Bmax (r = 0.9, r = 0.85). We conclude that chronic glucose infusion inhibits the development of beta-receptor binding in fetal lamb lung, and that this effect is greater in males than females. Such a mechanism could be a factor in the predisposition of infants of diabetic mothers to develop respiratory distress and could contribute to a male disadvantage in respiratory morbidity.
Warburton
D
D
Department of Pediatrics, University of Southern California School of Medicine, Children's Hospital, Los Angeles 90054.
Buckley
S
S
Parton
L
L
Saluna
T
T
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005947:Glucose / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood*; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012737:Sex Factors; D012756:Sheep
D001786:Blood Glucose; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D005947:Glucose