Summary
The extensive association of mammalian insulins in solution and the aggregation of insulin receptors in cell membranes are well documented. The hypothesis advanced here is that a direct connection exists between these observations. It is postulated that, after binding to its receptor, an insulin monomer can interact with another similarly bonded hormone-receptor complex through those groups on the insulin monomer faces utilized for dimer-dimer contacts in the crystal and in solution. Regarded thus, the insulin molecules are effectively bivalent as required for the formation of cross-links between receptors, with the accompanying enhancement of biological activity. A number of properties of native insulins from different animals, and of modified insulins, are considered in the light of this suggestion. It is shown to have considerable power in reconciling a diversity of such observations and to provide a plausible model for the experimentally observed receptor clustering phenomenon.
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Jeffrey, P.D. The interaction of insulin with its receptor: Cross-linking via insulin association as the source of receptor clustering. Diabetologia 23, 381–385 (1982). https://doi.org/10.1007/BF00260946
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DOI: https://doi.org/10.1007/BF00260946