Insulin binding and
insulin receptor down-regulation characteristics were evaluated, as well as
cholesterol and
phospholipid levels in erythrocytes from 22 patients with
liver cirrhosis. These parameters were correlated with clinical characteristics and with scores related to severity of the liver injury. Nine healthy subjects were studied as a control group. It was observed that
insulin binding was generally greater in patients than in controls because of an increase in surface
insulin receptor numbers, rather than from a change in receptor affinities. In cirrhotic patients, the erythrocyte
insulin receptors did not undergo the normal down-regulation process but, in most cases, increased in response to
insulin incubation. The alterations in
insulin processing characteristics were more frequent in patients with
alcoholic cirrhosis and more severe liver impairment and correlated with the changes in the
lipid composition of erythrocyte membranes. In particular, an increase in the
cholesterol to
phospholipid molar ratio and a decrease in
polyunsaturated fatty acid content of
phospholipids in erythrocyte membranes of cirrhotic patients was associated with impairments in
insulin receptor processing. Similar changes in
insulin receptor processing were observed when the molar ratio of
cholesterol to
phospholipid in normal erythrocytes was modified in vitro by incubation with
cholesterol-rich
liposomes.