Effect of IgG Subclasses on In Vivo Bioavailability and Metabolic Fate of Immune-Complexed Insulin in Lewis Rats

Abstract

The bioavailability, distribution, and metabolic fate of 125l-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig lgG1, lgG2, a mixture of lgG1 and lgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125l-insulin complexed to purified guinea pig lgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125l-insulin complexed to guinea pig lgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125l-insulin bound to lgG1 and lgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of 125l-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of lgG1 and lgG2 antibodies compared with the 125l-insulin complexed to either purified lgG1 or lgG2 antibodies alone. The 125l-insulin bound to antibodies in native guinea pig antiserum or a mixture of lgG1 and lgG2 antibodies was distributed invivo in a manner reflecting the relative concentrations of the lgG1 and lgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125l-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability, distribution, and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies.