Insulin is degraded extracellularly in wounds by insulin-degrading
enzyme (ec 3.4.24.56).
Shearer, Jeffry D., Cynthia F. Coulter, William C. Engeland, Richard
A. Roth, Michael D. Caldwell.
Center for Wound Healing and Reparative Medicine, Department of
Surgery, University of Minnesota, Minneapolis, MN 55455, Department
of Molecular Pharmacology, Stanford University School of Medicine,
Stanford, CA 94305-5332
APStracts 4:0138E, 1997.
The exact mechanism by which insulin reverses impaired wound healing
is unknown. Previous investigators have shown that insulin is
degraded in experimental wounds suggesting that the action of insulin
may be locally modified. The following study corroborates these
findings and identifies the major proteinase responsible for insulin
degradation in wound fluid (WF). Adult male Fisher rats were wounded
by subcutaneous implantation of polyvinyl alcohol sponges while under
sodium pentobarbital anesthesia. Wound fluid and serum were collected
on 1, 5, 10, and 14 days post-injury. Decreased insulin concentration
in late WF correlated with an increased insulin degrading activity.
Multiple proteinases appear to participate in the overall degradation
of insulin in WF. However, the primary enzyme responsible for insulin
degradation in WF was characterized by immunoprecipitation and
immunoblotting and identified as the neutral thiol-dependent
metalloproteinase, insulin-degrading enzyme (IDE; EC 3.4.24.56).
Exogenous steroid administration caused a decrease in WF insulin
degrading activity. Glucagon and adrenocorticotrophin (ACTH)
degradation was also observed, whereas minimal degradation of
insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and epidermal
growth factor (EGF) was detected in WF. The ability to
extracellularly degrade insulin may represent a unique mechanism for
the regulation of this hormoneOs role in healing wounds.
Received 13 January 1997; accepted in final form 19 January 1997.
APS Manuscript Number E45-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 10 July 1997