Primary Hyperinsulinemia Reduces Surface Active Material Flux in Tracheal Fluid of Fetal Lambs

Abstract

SummaryWe sought to test the hypothesis that hyperinsulinemia per se alters the flux of surface active material (SAM) into tracheal fluid by continuously infusing insulin (0.24 + 0.04 units/kg/hr, mean + S.E.) from 112 through 135 days gestation into five chronically catheterised fetal lambs, from which tracheal fluid could be collected.Serum insulin levels in these fetuses (95 f 10 pU/ml) were greater than in five chronically catheterised control fetuses of the same gestational age (10 f 1 pU/ml, P < 0.001) and in the mothers (33 + 6 pU/ml, P < 0.001). Serum glucose levels in the insulin-treated fetuses (10 k 1 mg/dl) were lower than in the control fetuses (19 + 1 mg/dl, P < 0.001) and in the mothers (60 f 3 mg/dl, P < 0.001). Arterial blood gases (pH 7.37 + 0.01, Po2 23.3 + 0.05 mm Hg, Pcoz 41.5 f 0.9 mm Hg) and hematocrit (33 + 1% at 127 days gestation and 31 + 1% at 135 days gestation) in the insulin treated fetuses were not different from the controls.SAM flux into the tracheal fluid of the insulin-treated fetuses was 1 pg/kg/hr, coefficient of variation 373%. This was lower than SAM flux in the control fetuses (26 pg/kg/hr, coefficient of variation 28%, P < 0.01). Moreover, among the control fetuses, SAM began to appear in tracheal fluid at 119 days gestation and was present in all five fetuses by 125 days gestation, whereas SAM did not begin to appear in the insulin-treated fetuses until 127 days gestation and did not appear at all in three of them. SpeculationChronic hyperinsulinemia reduces surface active material flux into tracheal fluid of fetal lambs. This effect may be partially mediated by reduced substrate (glucose) availability for surface active material phospholipid synthesis, storage, and/or secretion.The incidence of respiratory distress syndrome is reported by Robert et al. (21) to be increased almost 6-fold in infants of diabetic mothers, even when suitable corrections are made for gestational age. However, RDS may be less prevalent when maternal diabetes is mild and well controlled (7,8). The infants of diabetic mothers experiences hyperinsulinemia both in utero and in the postnatal period (2,10,12,16,22), particularly when glucose homeostasis is poor (24).Stubbs and Stubbs (28) have hypothesised that fetal hyperinsulinemia may be the common link between maternal diabetes mellitus and respiratory distress syndrome. Stubbs et al. (27) reported that the glucose uptake of isolated perfused rat lung increased by 30% in the presence of physiologic concentrations of ilisulin. Sosenko et al. (26) and Rhoades et al. (20) found evidence of delayed lung maturation in fetuses of glucose intolerant rabbits and rats respectively. Also, Smith et al. (23) found that, in the presence of glucocorticoids, lecithin synthesis by cultured fetal lung cells decreased in response to higher concentrations of insulin. In addition, Gross et al. (9) have indicated that insulin delays the morphologic maturation of fetal rat lung cultures, causing a decrease in the number of lamellar bodies and alveolar type I1 ce...

Chronic hyperglycemia with secondary hyperinsulinemia inhibits the maturational response of fetal lamb lungs to cortisol.

“…The control fetuses reported here underwent significant lung maturation in response to cortisol, as reflected by large and statistically significant increases in SAM flux into their tracheal fluid and in their tracheal fluid phospholipid content, which were much greater than those that occur between days 128 and 130 of gestation during normal maturation of fetal lamb lungs (10,11,23 The dose of cortisol infused to both glucose-treated and control fetuses (420 pg/h) was calculated to be approximately twice the cortisol production rate into an adrenal vein of term fetal lambs reported by Chester-Jones et al (25). Significant elevations in serum cortisol levels occurred in both control and glucosetreated fetuses to levels approximating those seen in the near-term fetal lamb (23).…”

“…Warburton (10,11) has reported that both primary hyperinsulinemia with concomitant hypoglycemia, and chronic hyperglycemia with secondary hyperinsulinemia reduce SAM flux into tracheal fluid of fetal lambs. Before 128 d gestation, SAM flux into tracheal fluid in the current experiment was similar to Warburton's previously reported data.…”

“…In the fetal lamb, infusion of insulin was reported by Warburton et al (10) to reduce the flux of surface active material (SAM) into tracheal fluid, in contrast to the sharp rise toward term in SAM flux into tracheal fluid of control fetuses. However, the insulin-treated fetal lambs in this study became hypoglycemic relative to controls.…”

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

“…Warburton et al (16) have recently reported that primary hyperinsulinemia reduces surface active material flux in tracheal fluid of fetal lambs in the presence of intrauterine hypoglycemia. Taken together with the results of the current study, these data implicate hyperinsulinemia as an etiologic factor in the reduction of SAM flux.…”

“…Warburton et al (16) recently reported that primary hyperinsulinemia reduces surface active material flux in tracheal fluid of fetal lambs. However, the insulintreated lambs in this study became hypoglycemic relative to controls.…”