Insulin inhibits beta-adrenergic responses in fetal rabbit lung in explant culture.
Infants of diabetic mothers are at increased risk of a number of problems at birth. Among these problems are increased risks of respiratory distress syndrome and transient tachypnea of the newborn. Because surfactant synthesis, surfactant secretion, and lung fluid resorption are all mediated in part by beta-adrenergic responses, we asked if excess insulin interferes with the beta-adrenergic response cascade in fetal lung. Lungs from fetal rabbits (26 day) were grown in explant culture in hormone-supplemented culture medium. The explants were harvested after 48 h exposure to hormones and processed for determination of beta-adrenergic receptor concentration, guanine nucleotide regulatory proteins (Gs, Gi), beta-agonist stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation, cAMP-dependent phosphodiesterase activity, and choline incorporation into phosphatidylcholine. Although insulin did not change the concentration of beta-adrenergic receptors, it decreased the ability of isoproterenol to stimulate cAMP generation. Increase in stimulation over basal was similar in explants treated with dexamethasone and dexamethasone plus insulin, but absolute levels of isoproterenol-stimulated cAMP were less in the explants treated with dexamethasone plus insulin. We speculate that insulin inhibition of cAMP generation may be important in the pathogenesis of the respiratory problems of infants of diabetic mothers.
Davis
D J
DJ
Department of Pediatrics, Emory University, Atlanta, Georgia 30322.
Hickman
J M
JM
Lefebvre
C A
CA
Lyon
M E
ME
D000818:Animals; D046508:Culture Techniques; D000242:Cyclic AMP / Q000096:biosynthesis / Q000502:physiology; D003720:Densitometry; D003907:Dexamethasone / Q000494:pharmacology; D005333:Fetus / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D007328:Insulin; D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D019204:GTP-Binding Proteins; D007545:Isoproterenol