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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 May;80(9):2757–2761. doi: 10.1073/pnas.80.9.2757

Nonenzymatic glucosylation of homologous low density lipoprotein and albumin renders them immunogenic in the guinea pig.

J L Witztum, U P Steinbrecher, M Fisher, A Kesaniemi
PMCID: PMC393907  PMID: 6405389

Abstract

Nonenzymatic glucosylation of low density lipoprotein (LDL) and other plasma and structural proteins is enhanced in diabetics. Because conjugated carbohydrates are known to play an important role in the immunogenicity of proteins, we sought to determine if glucosylation of LDL (yielding Glc-LDL) and albumin would make them immunogenic. Therefore, we immunized guinea pigs with homologous glucosylated proteins and measured antibody response by solid-phase radioimmunoassay. Glucosylation of LDL in the presence of cyanoborohydride yields glucitol-lysine as the glucose adduct. Immunization with this Glc-LDL yielded a high-titered antiserum that reacted specifically with guinea pig Glc-LDL but not native LDL. Glucitol-lysine was an effective competitor for binding to the antibody, as were other reductively glucosylated human proteins. Glucosylation of LDL by incubation with glucose in the absence of a reducing agent yields fructosyllysine as the glucose adduct. This product, which has been demonstrated in human plasma, was also immunogenic, though the antiserum produced was of lower titer and affinity. Homologous glucosylated albumin was also immunogenic. These data suggest that nonenzymatic glucosylation of proteins could lead to autoantibody production and the formation of immune complexes in diabetic plasma and tissues.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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