Insulin acts on the fibroblast to inhibit glucocorticoid stimulation of lung maturation

Abstract

The effects of insulin and cortisol on saturated phosphatidylcholine synthesis are examined in fetal type II cell cultures and in mixed cell cultures containing type II cells and fibroblasts. In 19-day fetal rat lung type II cell cultures, 100 nM cortisol and 2 nM insulin have no significant effect. Fibroblast-pneumonocyte factor results in enhanced saturated phosphatidylcholine synthesis by fetal type II cells. The significant stimulatory effect of cortisol in mixed-cell cultures is abolished in the presence of insulin or of monoclonal antibodies to fibroblast-pneumonocyte factor. Incubation of type II cells with conditioned media from fibroblasts exposed to cortisol results in increased saturated phosphatidylcholine synthesis. This process is not stimulated when type II cells are incubated with conditioned media from fibroblasts exposed to insulin and cortisol (or to insulin alone). These observations demonstrate that insulin inhibits cortisol induction of lung maturation and suggest that this antagonism results from an inhibitory effect of insulin on the elaboration of fibroblast-pneumonocyte factor by fetal lung fibroblasts.

Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of Women at Risk of Imminent Preterm Birth: A Systematic Review and Meta-Analysis

“…Without appropriate monitoring and adjustment of insulin dosage, this, in turn, may create an increased risk of severe dysregulation with ketoacidosis. With maternal hyperglycaemia, fetal lung development may also be compromised [ 59 ], potentially offsetting any benefits of ACS therapy to the infant. However, direct evidence for this is lacking.…”

Delayed Maturation of Fetal Lung in Yellow KK Mice

“…Corticoids accelerate fetal lung maturation and cause alveolar wall thinning, alteration of alveolar wall composition, and an increase in the volume of air spaces (Kikkawa et al, 1971;Massaro and Massaro, 1986) as well as biochemical lung maturation as shown by glycogen deposition and surfactant synthesis (Rooney et al, 1986;Juanes et al, 1986). On the other hand, insulin is known to inhibit fetal lung maturation because insulin antagonizes the action of corticoid (Carlson et al, 1984;Smith et al, 1975). Therefore, delayed maturation of the lung in the fetuses from diabetic dams may be due to fetal hyperglycemia, hyperinsulinemia, or both.…”

Antenatal glucocorticoids: where are we after forty years?

“…45 Antenatal glucocorticoid therapy causes a transient increase in maternal glucose concentrations, [46][47][48] often more pronounced in women with diabetes, 46,49 and some 47 but not all 50 randomized trials have shown an increase in the incidence of glucose intolerance in women following glucocorticoid administration. While hyperglycemia and hyperinsulinism can impair glucocorticoid action, [51][52][53] outcomes appear similar for preterm infants of mothers with and without diabetes when there is adequate maternal glycemic control and a high rate of antenatal glucocorticoid exposure. 54,55 Consequently, antenatal glucocorticoid therapy remains indicated in women with diabetes, 11 although increased insulin therapy may be required.…”