AJP - Lung Cellular and Molecular Physiology, Vol 263, Issue 5 562-L567, Copyright © 1992 by American Physiological Society
Insulin inhibits beta-adrenergic responses in fetal rabbit lung in explant culture
D. J. Davis, J. M. Hickman, C. A. Lefebvre and M. E. Lyon
Department of Pediatrics, Emory University, Atlanta, Georgia 30322.
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.
