Increased fetal insulin receptors and changes in membrane fluidity and lipid composition.

Fetal tissues exposed to hyperinsulinemia in utero have significantly greater numbers of insulin receptors than do those of controls. We have studied this upregulation phenomenon using crude microsomal membranes from fetal rabbit litters exposed to varying degrees of hyperinsulinemia in diabetic pregnant rabbits. We have observed that insulin binding capacity of membranes increased directly with the severity of maternal diabetes, ranging from 8.5 ng in controls to 44.6 ng insulin/mg membrane protein in offspring of severely diabetic animals and related directly with increasing fetal insulin levels (r = 0.77, P less than 0.005). Lipid analyses of fetal lung membranes showed that reduction of phospholipid to protein ratios occurred in the presence of maternal diabetes. Membrane cholesterol-to-phospholipid ratios were also altered in the presence of maternal diabetes. Significantly, increases in plasma membrane microviscosity were noted in the membranes from diabetic offspring. The data suggest that reduction of membrane fluidity is associated with increases in fetal membrane insulin receptors in severely diabetic pregnancies.