Modulation of binding and bioactivity of insulin by anti-insulin antibody: relation to possible role of receptor self-aggregation in hormone action.
Incubation of physiological concentrations of 125I-labeled insulin with liver membranes in the presence of anti-insulin IgG results in a 7- to 15-fold increase in the specific binding of the hormone. The low-affinity/high-capacity binding sites are replaced by an apparently homogeneous class of high-affinity sites, and the nonlinear Scatchard plots are converted to linear plots without a change in the maximum number of binding sites. Similarly, the binding of insulin to receptors in 3T3 fibroblasts is increased substantially in the presence of anti-insulin antibody, and the biological activity of subactive concentrations of insulin is enhanced by antibody in these cells. However, the affinity of 125I-labeled epidermal growth factors (EGF) in fibroblasts is not affected by anti-EGF IgG. In adipocytes anti-insulin IgG in the same concentration range only inhibits the binding of insulin and suppresses insulin-mediated glucose oxidation. Monovalent Fab' fragments from anti-insulin IgG inhibit the binding of the hormone, indicating that the enhancement of binding in liver membranes and fibroblasts requires the bivalency of the antibody.
D000818:Animals; D000936:Antigen-Antibody Complex; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007328:Insulin / Q000378:metabolism*; D007330:Insulin Antibodies; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D011972:Receptor, Insulin / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007328:Insulin; D007330:Insulin Antibodies; D011972:Receptor, Insulin