Autoantibodies to the insulin receptor. Effect on the insulin-receptor interaction in IM-9 lymphocytes.
The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of (125)I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins. The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as unique probes of insulin receptor structure and function.
D000494:Allosteric Regulation; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies; D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D007106:Immune Sera; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D011972:Receptor, Insulin / Q000276:immunology* / Q000378:metabolism; D013696:Temperature
D001323:Autoantibodies; D007106:Immune Sera; D007328:Insulin; D011972:Receptor, Insulin