Glucagon-like peptide-1 undergoes differential tissue-specific
metabolism in the anesthetized pig.
Deacon, Carolyn F, Lone Pridal, Letty Klarskov, Mette Olesen, and Jens
J Holst.
Department of Medical Physiology, Panum Institute, and Department
of Experimental Pathology, Rigshospitalet, University of Copenhagen,
and Department of Diabetes Pharmacology, Novo Nordisk A/S, Bagsvaerd,
Denmark
APStracts 3:0105E, 1996.
Glucagon-like peptide-1 (GLP-1) metabolism was studied in halothane
-anesthetized pigs (n=7) using procesing-independent (PI-RIA) and C
-terminal (C-RIA) radioimmunoassays and an enzyme-linked immunosorbant
assay (ELISA) specific for biologically active GLP-1. Renal
extraction of endogenous GLP-1 was detected by PI-RIA (33.1+/-13.3%)
and C- RIA (16.0+/-6.3%), and by all assays during GLP-1 infusion
(ELISA, 69.4+/-6.3%; PI-RIA, 32.6+/-7.3%; C-RIA, 43.7+/-3.4%),
indicating substantial fragmentation. Hepatic and pulmonary
degradation were undetectable under basal conditions, but exogenous
GLP-1 elimination by the liver (43.6+/-8.9%) and lungs (10.1+/-3.2%)
was measured by ELISA, suggesting primarily N-terminal degradation.
Endogenous GLP-1 extraction by the hindleg was only detected by C-RIA
(16.0+/-6.3%). During GLP-1 infusion, greater hindleg extraction was
measured by ELISA (38.5+/-6.8%) and C-RIA (33.0+/-6.4%) than by PI
-RIA (11.4+/-3.2%), indicating limited degradation at each terminus or
more substantial C-terminal degradation. A shorter (P < 0.01)
plasma half-life was revealed by ELISA (1.5+/-0.4 min) than by PI-RIA
(4.5+/-0.6 min) or C-RIA (4.1+/-0.5 min). Metabolic clearance rates
measured by PI-RI (20.0+/-3.8 ml/min/kg) and C-RIA (15.5+/-1.6
ml/min/kg) were shorter (P < 0.01) than that measured by ELISA
(106.8+/-14.7 ml/min/kg). Tissue-specific differential metabolism of
GLP-1 occurs, with N-terminal degradation rendering GLP-1 inactive
being particularly important in its clearance.
Received 18 December 1995; accepted in final form 7 May 1996.
APS Manuscript Number E586-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96