AJP - Endocrinology and Metabolism, Vol 272, Issue 6 E1136-E1144, Copyright © 1997 by American Physiological Society
An evaluation of the cross-linking model for the interaction of insulin with its receptor
B. J. Hammond, J. Tikerpae and G. D. Smith
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, United Kingdom.
The cross-linking model for insulin receptor interactions, in which a
single insulin molecule may form a cross-link between an insulin receptor's
alpha-subunits, has been expressed as a formal compartmental model and
subjected to a systematic analysis, examining a number of predictions that
have been made for this model. The kinetic parameters for the model were
obtained by matching data from insulin receptor equilibrium binding studies
and rates of formation of the insulin receptor complex. This analytical
study has allowed a clear description of the kinetics of the ligand
receptor complexes involved in such a mechanism. We conclude that the
cross-linking model accounts for the anomaly of the 10-fold concentration
difference in high- and low-affinity binding sites found when insulin
binding is analyzed by conventional means. However, the phenomenon of
acceleration of dissociation of labeled ligand by unlabeled ligand cannot
be accounted for as an intrinsic part of the model. We suggest that this
phenomenon arises from the destabilization of cross-link formation when a
second insulin molecule binds.
