The Influence of Hormones on the Biochemical Development of Fetal Rat Lung in Organ Culture. II. Insulin

Abstract

Summary ated species of this phospholipid is believed to play a major role In lowering surface tension at the air-alveolar interface, thereby PC in the lungs of the fetuses of glucose-intolerant monkeys. InInsulin treatment had no effect on the rate of choline incorpoaddition, Moxley and L~~~~~~~ found ,hat glucose ration into phosphatidylcholine (PC) or disaturated PC and did into PC in isolated, perfused rat lungs was decreased not antagonize the dexamethasone-induced stimulation of choline when the lungs of adult diabetic rats were used. These effects incorporation into PC. When the incorporation of IVilacetate into be reversed by insulin treatment prior to perfusion. the various phospholipid fractions was examined, however, i t was of insulin action. which depend on isotope incorporation into found that exposure to insulin resulted i n a significant decrease i n phospholipids. are, however. complicated by t h e fact insulin the percentage of phospholipid radioactivity in the disaturated PC [he uptake of some substrates into cells and may also fraction and an increase i n the percentage of radioactivity i n the influence the intracellular pool size of these substrates, had the nppnsite effect to insulin with regard to acetate incorpo-phol,p,ds other than PC. was ~h~~~ included the imration into the various phospholipid fractions, and when the two portant surfactant components disaturated PC and phosphatidylhormones were combined, this effect was diminished or abolished. glycerol ( 19. I ) as well as the phosphol,p,dh usually The effects of insulin could not be accounted for on the basis of a with cell membranes. mono-and unsaturated PC.. phosphatidylchange i n activity of any of the enzymes of phospholipid synthesis elhanolamine, phosphat,dylinositol. phosphatidylserine. and that were examined. sphingomyelin (27). The influence of insulin on enzymes involvedThese findings suggest that insulin stimulates the synthesis of with pulmonary phospholipid synthesis was also examined, the cell membrane phospholipids while decreasing that of the surfactant phospholipid, disaturated PC.

The effect of maternal diabetes on the synthesis and secretion of phosphatidylcholine in fetal and maternal rat lungs in vitro

“…During maternal diabetes, the fetus is exposed to hyperglycaemia and hyperinsulinaemia [37][38][39][40], both of which inhibit glycogenolysis and lower synthesis of surfactant phospholipids in fetal lungs [9,11,12]. In the present study, rat fetuses were exposed to hyperglycaemia which subsided to almost normal serum glucose levels in newborn after parturition (Table 1).…”

“…Synthesis of surfactant phospholipids appears to be dependent on metabolism of glucose [3][4][5] and glycogen [6][7][8][9] as they provide dihydroxyacetone phosphate and a-glyceraldehyde phosphate, which are precursors of phospholipid synthesis in lungs [6,9,10]. In maternal diabetes, the fetus is exposed to hyperglycaemia and hyperinsulinaemia both of which inhibit glycogenolysis Present address: * Department of Crop Science, University of Saskatchewan, Saskatoon, Saskatchewan Canada, S7N 0W0 9 * Faculty of Medicine, University of Manitoba, Winnipeg, Canada R3E 0W3 and reduce the formation of precursors for synthesis of surfactant phospholipids [9,[11][12][13]. While some investigators have reported reduced synthesis of surfactant phospholipids in lungs of fetuses of diabetic mothers [14,15] others have not observed any significant changes in the phospholipid synthesis [16,17].…”

Effects of Insulin and Glucose on Pulmonary Insulin Receptors in Late Gestation Fetal Rats

“…Many studies implicate insulin as an inhibitor of fetal lung maturation [6,71, although data are not consistent [8, 91. Substrate availability is important in fetal lung differentiation.…”

Chronic Hyperglycemia Reduces Surface Active Material Flux in Tracheal Fluid of Fetal Lambs

“…Gross et al (10) have reported that insulin delays the morphologic maturation of fetal rat lung in organ culture, causing a decrease in the number of lamellar bodies in alveolar type II cells. In addition, Smith et al (11) have reported that insulin inhibits lecithin synthesis by cultured mixed fetal lung cells in the presence of glucocorticoids.…”