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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
. 1978 Sep;75(9):4209–4213. doi: 10.1073/pnas.75.9.4209

Direct demonstration that receptor crosslinking or aggregation is important in insulin action

C Ronald Kahn 1, Kathleen L Baird 1, David B Jarrett 1, Jeffrey S Flier 1
PMCID: PMC336081  PMID: 279910

Abstract

Exposure of adipocytes to antibodies to the insulin receptor results in a blockade of 125I-labeled insulin binding, stimulation of glucose oxidation, and many more insulin-like effects. Allowing for differences in purity, antireceptor antibody is equipotent with insulin on a molar basis. Both the bivalent F(ab′)2 and monovalent Fab′ fragments of the antireceptor antibody are fully active in inhibiting 125I-labeled insulin binding. Bivalent F(ab′)2 also retains its insulin-like effects. In contrast, the monovalent Fab′ loses almost all ability to stimulate glucose oxidation and acts as a competitive antagonist of insulin-stimulated glucose oxidation. Addition of anti-F(ab′)2 antisera, which crosslink the Fab′-receptor complexes, results in a restoration of the insulin-like activity of the antibody. Similarly, when cells are exposed to submaximal doses of insulin, addition of anti-insulin antibodies at low concentration enhances the biological activity of insulin. These data suggest that receptor occupancy by ligand is not sufficient for signal generation and that the insulin-like effects of antireceptor antibody (and perhaps insulin itself) require receptor aggregation or clustering. This aggregation, however, appears to be independent of microfilaments or microtubules because the insulin-like effects of antireceptor antibody, and in fact, of insulin itself, are unaffected by agents that are known to disrupt these structures.

Keywords: insulin receptor, receptor antibody, competitive antagonist, insulin antibody, membranes

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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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