Effect of Isologous and Autologous Insulin Antibodies on In Vivo Bioavailability and Metabolic Fate of Immune-Complexed Insulin in Lou/M Rats

The in vivo bioavailability, distribution, and metabolic fate of ¹²⁵I-labeled insulin complexed to isologous and autologous antibodies were studied in inbred Lou/M rats. There was an impaired bioavailability of the ¹²⁵I-insulin bound to the isologous and autologous antibodies. Very little of the ¹²⁵I-insulin in these immune complexes could bind to insulin receptors on hepatocytes or renal tubular cells and be degraded, because the amounts of ¹²⁵I from degraded ¹²⁵I-insulin in the blood or secreted into the stomach were markedly attenuated in both cases for at least 30 min after injection. There was a simultaneous accumulation of ¹²⁵I-insulin immune complexes in the liver and the kidneys of Lou/M rats injected with ^,25I-insulin complexed with isologous antibodies or when insulin-immunized Lou/M rats were injected with ¹²⁵I-insulin during the same interval. The impaired bioavailability of immune-complexed insulin and altered distribution of radioactivity due to the accumulation of immune complexes in the liver and kidney were also observed in previous experiments in which Lewis rats were injected with xenogenic guinea pig and homologous insulin antibodies. These observations are therefore submitted as evidence that the Lou/M rat is a valid model in which to study the bioavailability of insulin immune complexed to isologous, homologous, and xenogenic antibodies and the metabolic fate of the respective insulin-antibody immune complexes.