Influence of the Lipid Environment on Insulin Binding to Placental Membranes from Normal and Diabetic Mothers

Abstract

It is generally accepted that the function of membrane proteins is affected by the fluidity of the membrane (Sandermann, 1978; Kates and Kuksis, 1980; Shinitzky et al., 1980; Chapman, 1983). Temperature (Lee, 1977), the protein to lipid content (Shinitzky et al., 1980) and the lipid composition (Phillips et al., 1969; Borochov et al., 1979) are the major determinants of membrane fluidity. Effects of fluidity on receptor specificity and affinity have been reported for the thyrotropin receptor (Mehdi et al., 1977; Lee et al., 1978), for the serotonin receptor (Heron et al., 1980) and for the insulin receptor (Amatruda and Finch, 1979; Grunfeld et al., 1981; McCaleb and Donner, 1981; Ginsberg et al., 1981; Gould et al., 1982; Bar et al., 1984). The studies directed to the modulation of membrane proteins by the lipid environment have been accomplished on cultured cells by dietary manipulations leading to a modification of either the fatty acid composition or phospholipid headgroups. Corresponding studies with isolated membranes used physical techniques which altered the bulk fluidity of the membrane or by treatment of the membranes with phospholipases (Gould and Ginsberg, 1984). In the present study we chose a different approach. The affinity of insulin receptors from various tissues has been repeatedly shown to be altered in diabetes mellitus (Andreani et al., 1981). We analyzed the insulin receptors in placental membranes from normal and diabetic mothers and correlated the receptor affinities with parameters which are known to determine membrane fluidity. Thus, we did not study the insulin receptor system in an artificially altered lipid environment but investigated how the receptor affinity is affected by an in vivo modification of the membrane as a result of a pathological state.