Gross structural changes in isolated liver cell plasma membranes upon binding of insulin

Abstract

The addition of 10-9 M insulin to a suspension of rat liver plasma membranes increases the overall lipid microviscosity .hivin..eta., by about 10-20%. The effect is confined to physiological concentrations of the hormone and is highly specific. The specificity was demonstrated in experiments where insulin analogs were added to liver plasma membranes and where insulin was added to human erythrocyte membranes. In both of these experiments practically no change in .hivin..eta. was detected. Upon in vitro enrichment of the membrane cholesterol, .hivin..eta. exceeded the level mediated by insulin binding, and the addition of 10-9 M insulin to the cholesterol-enriched membranes did not further increase .hivin..eta.. Concomitant to the increase in .hivin..eta. upon insulin binding, the overall degree of exposure of the membrane protein, presumably to both sides of the membrane, is substantially increased. This effect is in line with the notion of vertical displacement of membrane proteins induced by changes in .hivin..eta.. The observed structural modulation can account for the effect of insulin on unrelated membrane responses, as well as for the negative cooperativity of insulin binding.