Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats.
The bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125I-insulin bound to IgG1 and IgG2 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 125I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the 125I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The 125I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125I-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.
Arquilla
E R
ER
Department of Pathology, University of California, Irvine 92717.
Stenger
D
D
McDougall
B
B
Ulich
T R
TR
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001682:Biological Availability; D005753:Gastric Mucosa / Q000378:metabolism; D006168:Guinea Pigs; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007328:Insulin / Q000031:analogs & derivatives / Q000276:immunology / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011972:Receptor, Insulin / Q000378:metabolism; D014018:Tissue Distribution
D000936:Antigen-Antibody Complex; D007106:Immune Sera; D007074:Immunoglobulin G; D007328:Insulin; D007457:Iodine Radioisotopes; C008147:insulin, iodo-; D011972:Receptor, Insulin