An evaluation of the cross-linking model for insulin-receptor
interactions.
Hammond, Bruce J., Jaak Tikerpae, and Geoffrey D. Smith.
University of Cambridge, Dept. Clinical Biochemistry, Addenbrooke's
Hospital, Hills Road, Cambridge CB2 2QR, UK.
APStracts 4:0043E, 1997.
_The cross-linking model for insulin-receptor interactions, where a
single insulin molecule may form a cross-link between an insulin
receptors [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
obtained 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 analysed by conventional means. However, the
phenomenon of acceleration of dissociation of labelled ligand by
unlabelled ligand cannot be accounted for as an intrinsic part of the
model. We suggest that this phenomenon arises from the
destabilisation of cross-link formation when a second insulin
molecule binds. (Accepted for the Modeling in Physiology section)
Received 6 September 1996; accepted in final form 30 January
1997.
APS Manuscript Number E448-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 20 February 1997