Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats

Journal Article · Thu Oct 01 04:00:00 EDT 1987 · Diabetes; (United States)

DOI:https://doi.org/10.2337/diab.36.10.1144· OSTI ID:5628958

Arquilla, E R; Stenger, D; McDougall, B; Ulich, T R

The bioavailability, distribution, and metabolic fate of /sup 125/I-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. /sup 125/I-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 /sup 125/I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of /sup 125/I-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 /sup 125/I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the /sup 125/I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The /sup 125/I-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 /sup 125/I-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.

• Research Organization: Univ. of California, Irvine
• OSTI ID: 5628958
• Journal Information: Diabetes; (United States), Journal Name: Diabetes; (United States) Vol. 36:10; ISSN DIAEA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL AVAILABILITY
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
GASTROINTESTINAL TRACT
GLANDS
GLOBULINS
GUINEA PIGS
HORMONES
IMMUNOGLOBULINS
IN VIVO
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIVER
MAMMALS
MEMBRANE PROTEINS
METABOLISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
STOMACH
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES