title: Direct demonstration that receptor crosslinking or aggregation is important in insulin action.
abstract: Exposure of adipocytes to antibodies to the insulin receptor results in a blockade of (125)I-labeled insulin binding, stimulation of glucose oxidation, and many more insulin-like effects. Allowing for differences in purity, antireceptor antibody is equipotent with insulin on a molar basis. Both the bivalent F(ab')(2) and monovalent Fab' fragments of the antireceptor antibody are fully active in inhibiting (125)I-labeled insulin binding. Bivalent F(ab')(2) also retains its insulin-like effects. In contrast, the monovalent Fab' loses almost all ability to stimulate glucose oxidation and acts as a competitive antagonist of insulin-stimulated glucose oxidation. Addition of anti-F(ab')(2) antisera, which crosslink the Fab'-receptor complexes, results in a restoration of the insulin-like activity of the antibody. Similarly, when cells are exposed to submaximal doses of insulin, addition of anti-insulin antibodies at low concentration enhances the biological activity of insulin. These data suggest that receptor occupancy by ligand is not sufficient for signal generation and that the insulin-like effects of antireceptor antibody (and perhaps insulin itself) require receptor aggregation or clustering. This aggregation, however, appears to be independent of microfilaments or microtubules because the insulin-like effects of antireceptor antibody, and in fact, of insulin itself, are unaffected by agents that are known to disrupt these structures.
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D003599:Cytoskeleton / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments; D007328:Insulin / Q000378:metabolism; D008024:Ligands; D008870:Microtubules / Q000378:metabolism; D011972:Receptor, Insulin / Q000276:immunology / Q000378:metabolism*
chemical_list: D007140:Immunoglobulin Fab Fragments; D007328:Insulin; D008024:Ligands; D011972:Receptor, Insulin; D005947:Glucose