Hyaline membrane disease of the newborn remains a significant clinical problem. The objective of this proposal will be to examine substrate and endocrine influences that may delay or accelerate lung maturation. We will study lung development inhyperglycemic fetuses of streptozotocin induced diabetic rats and will examine further the regulation of glycogen metabolism in developing lung and its relationship to the development of surfactant phospholipids. We have shown that fetuses of diabetic animals have a developmental delay in both lung glycogen degradation and surfactant phospholipid synthesis. Fetuses of diabetic animals are hyperglycemic but have normal insulin levels. We speculate that the developmental delay is related to hyperglycemia per se. Since insulin levels may not totally reflect influences on glucose flux into cells, we will measure insulin receptors on lung cell membranes of fetuses of diabetic animals and controls. We will also examine the influences of insulin, glucocorticoid, adrenergic agents and somatostatin on glycogen and phospholipid metabolism in fetuses of normal and diabetic mothers. Data will be correlated with activities of enzymes of phospholipid synthesis and fatty acid synthesis. We will also investigate endocrine and substrate influences on growth and carbohydrate and phospholipid metabolism of isolated type II cells from fetal and newborn rats. These cells will be utilized to examine regulatory influences on phospholipid synthesis including effects of hormones and growth factors. Epidermal growth factor (EGF) is of particular interest and we will examine its influences on type II cell growth and on glycogen and phospholipid metabolism. Morphological correlates of endocrine and growth factor influences on developing lung and on isolated cells will be sought at the light and electron microscopic level. These studies should continue to provide new information concerning substrate and endocrine influences on developing lung.
