Effect of antibody-mediated crosslinking of insulin on its bioactivity and receptor binding.
Precipitating anti-insulin antibodies or anti-insulin IgG/anti-IgG complexes bind insulin in a highly aggregated form and thus should preferably be capable of inducing receptor aggregation, which has recently been suggested to be a precondition for insulin bioactivity. We, therefore, studied the influence of antibody-mediated crosslinking of insulin on the glucose conversion into CO2 in rat fat cells and glycogen synthesis in rat liver cells. As far as possible receptor-bound insulin was measured in parallel. Insulin bound to antibodies with low insulin precipitating capacity had no or little bioactivity and receptor reactivity on fat cells. The bioactivity, however, could be restored in part by addition of a second antibody. On liver cells, second antibody-mediated crosslinking of insulin-antibody complexes resulted in an enhancement of receptor reactivity, and insulin bioactivity of such crosslinked immune complexes was demonstrable. An insulin-precipitating antiserum was shown to form insulin-antibody complexes with significant bioactivity in fat cells which correlated with their receptor binding. In each case antibodies had no or little effect in the absence of insulin. Our data suggest that insulin neutralization by antibodies can be compensated by crosslinking the insulin-antibody complexes or by formation of big complexes precipitating by themselves. This is probably due to the induction of receptor aggregation.
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000502:physiology*; D006003:Glycogen / Q000096:biosynthesis; D006168:Guinea Pigs; D007106:Immune Sera / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011940:Receptor Aggregation; D011972:Receptor, Insulin / Q000378:metabolism*
D000906:Antibodies; D007106:Immune Sera; D007328:Insulin; D006003:Glycogen; D011972:Receptor, Insulin