Insulin stimulates cell surface aminopeptidase activity toward
vasopressin in adipocytes.
Herbst, John J., Stuart A. Ross, Hazel M. Scott, Stephen A. Bobin,
Nicholas J. Morris, Gustav E. Lienhard, and Susanna R. Keller.
Department of Biochemistry, Dartmouth Medical School, Hanover, NH
03755
APStracts 3:0267E, 1996.
We previously discovered that insulin stimulates the marked
translocation of a novel membrane aminopeptidase, designated vp165,
to the cell surface in adipocytes. To examine the hypothesis that
this enzyme acts on peptide hormones, we assessed the relative
affinity of the enzyme for 22 peptide hormones by measuring the
inhibitory effect of each on the hydrolysis of a fluorogenic
substrate, and we directly assayed the cleavage of four of these.
Angiotensin III, angiotensin IV and lys-bradykinin bound to the
enzyme with half-saturation constants between 20 and 600 nM and were
cleaved by vp165. Vasopressin bound with lower affinity, but at
saturation was cleaved more rapidly. Subsequently, the effect of
insulin upon the rates of cleavage of 125I vasopressin by intact 3T3
-L1 and rat adipocytes was determined. With both cell types,
vasopressin cleavage was stimulated approximately 3-fold. These
findings indicate that a physiological role for vp165 may be the
processing of peptide hormones and that insulin could enhance the
cleavage of extracellular substrates by eliciting the translocation
of vp165 to the cell surface.
Received 8 August 1996; accepted in final form 3 December 1996.
APS Manuscript Number E382-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996