Effects of maternal diabetes on the levels, synthetic rates and activities of synthetic enzymes of surface-active phospholipids in perinatal rat lung.
Streptozotocin-induced maternal diabetes in the rat has been found to reduce selectively the content and synthetic rates of disaturated phosphatidylcholine and lysophosphatidylcholine in the lungs of term fetuses. Furthermore, the elevations in these parameters which occur during normal pulmonary maturation between the final gestational day and the first neonatal day are abolished or markedly curtailed, resulting in significantly reduced levels and synthetic rates of surfactant and its immediate precursor in the neonatal lung. In addition, complete or partial inhibition of the perinatal developmental rise in the activities of key enzymes catalyzing de novo phosphatidylcholine synthesis in the lung, viz., cholinephosphate cytidylyltransferase and cholinephosphotransferase, and of enzymes catalyzing reacylation of unsaturated to disaturated phospholipid, viz., lysophosphatidic acid and lysophosphatidylcholine acyltransferases, has been observed, resulting in reduced activities of these enzymes in the neonate. The observed reductions in surface-active phospholipid synthesis in the lungs of offspring of diabetic mothers may be related to these lowered enzyme activities, as well as to deficiencies in carbohydrate precursors available for phospholipid synthesis, as reported in previous studies. It is suggested that the hyperinsulinemia manifested in fetuses of diabetic mothers opposes the tendency of corticosteroids to enhance surface-active phospholipid synthesis, resulting in pulmonary surfactant deficiency and thus the propensity for neonatal respiratory distress.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002384:Catalysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D010743:Phospholipids / Q000096:biosynthesis*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000201:enzymology*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats
D010743:Phospholipids; D011663:Pulmonary Surfactants