Supraphysiologic glucose inhibits structural and functional fetal lung maturation in vitro. We have previously found that glucose treatment of fetal rat lung explants results in a decreased ratio of type II cell lamellar bodies to lipid inclusions in adjacent fibroblasts, leading us to speculate that hyperglycemia inhibits the “trafficking” of triglyceride (TG) from fibroblasts to type II cells, in turn leading to decreased surfactant phospholipid synthesis. Trafficking of triglycerides from fibroblasts to type II cells is a cell-mediated mechanism requiring active uptake of triglyceride by fibroblasts followed by (type II cell-derived) prostaglandin E2 stimulated release. To test this hypothesis we initially studied the effect of glucose (100mM) on the transfer of radiolabeled TG from 20-day fetal rat lung fibroblasts to type II cells in organotypic culture.

High glucose concentrations reduced the incorporation of 3H-TG into3 H-disaturated phosphatidylcholine by 60±8% (p<.05) and into3 H-phosphatidylglycerol by 87±3% (p<0.01). To localize the defect in TG transfer, we next examined the effects of glucose on the cell-mediated transit of TGs from the extracellular space to fibroblasts, and from fibroblasts to type II cells. Uptake of TG by fibroblasts and type II cells was unaffected by glucose exposure, but release of TG in response to PGE2 (200 ng/ml/15 hours) was significantly inhibited (48±5%, p<01), consistent with our morphological data in which TG appeared to be“trapped” within fibroblasts. These data provide a cellular mechanism for glucose-inhibited pulmonary surfactant production and further support the physiologic role of neutral lipid trafficking in pulmonary surfactant production.