Linked Life Data

11834453

Source:http://linkedlifedata.com/resource/pubmed/id/11834453

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-2-8
pubmed:abstractText
The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are degraded by dipeptidyl peptidase IV (DPP IV), thereby losing insulinotropic activity. DPP IV inhibition reduces exogenous GLP-1 degradation, but the extent of endogenous incretin protection has not been fully assessed, largely because suitable assays which distinguish between intact and degraded peptides have been unavailable. Using newly developed assays for intact GLP-1 and GIP, the effect of DPP IV inhibition on incretin hormone metabolism was examined. Conscious dogs were given NVP-DPP728, a specific DPP IV inhibitor, at a dose that inhibited over 90% of plasma DPP IV for the first 90 min following treatment. Total and intact incretin concentrations increased (P<0.0001) following a mixed meal, but on control days (vehicle infusion), intact peptide concentrations were lower (P<0.01) than total peptide concentrations (22.6 +/- 1.2% intact GIP; 10.1 +/- 0.4% intact GLP-1). Following inhibitor treatment, the proportion of intact peptide increased (92.5 +/- 4.3% intact GIP, P<0.0001; 99.0 +/- 22.6% intact GLP-1, P<0.02). Active (intact) incretins increased after NVP-DPP728 (from 4797 +/- 364 to 10 649 +/- 106 pM x min for GIP, P<0.03; from 646 +/- 134 to 2822 +/- 528 pM x m in for GLP-1, P<0.05). In contrast, total incretins fell (from 21 632 +/- 654 to 12 084 +/- 1723 pM x min for GIP, P<0.002; from 5145 +/- 677 to 3060 +/- 601 pM x min for GLP-1, P<0.05). Plasma glucose, insulin and glucagon concentrations were unaltered by the inhibitor. We have concluded that DPP IV inhibition with NVP-DPP728 prevents N-terminal degradation of endogenous incretins in vivo, resulting in increased plasma concentrations of intact, biologically active GIP and GLP-1. Total incretin secretion was reduced by DPP IV inhibition, suggesting the possibility of a feedback mechanism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
172
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
355-62
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs.
pubmed:affiliation
Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. deacon@mfi.ku.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't