Degradation paradigm of the Gut Hormone, Pancreatic Polypeptide, by hepatic and renal peptidases
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Pancreatic polypeptide (PP) is a gut hormone that acts on Y4 receptors to reduce appetite. Obese humans display a reduced postprandial rise in PP and remain fully sensitive to the anorectic effects of exogenous PP. The utility of PP as an antiobesity treatment is limited by its short circulating half-life. Insight into the mechanisms by which PP is degraded may aid design of long-acting PP analogues.We aimed to investigate the role of peptidases in PP degradation with a view to determining whether inhibition of these enzymes enhanced PP plasma levels and bioactivity in vivo. DPPIV and neprilysin (NEP) were two peptidase found to cleave PP. Limiting the effect of both peptidases improved the in vivo anorectic effect of PP and PP-based analogues. These studies suggest that inhibiting the degradation of PP using specific inhibitors and/or the design of analogues resistant to cleavage by DPPIV and NEP may be useful in the development of PP as an anti-obesity pharmacotherapy.
Date Issued
2017-03-09
Date Acceptance
2017-03-03
Citation
Endocrinology, 2017, 158 (6), pp.1755-1765
ISSN
1945-7170
Publisher
Endocrine Society
Start Page
1755
End Page
1765
Journal / Book Title
Endocrinology
Volume
158
Issue
6
Copyright Statement
© 2017 The Author(s). This article has been published under the terms of the Creative Commons Attribution
License (CC BY;
https://creativecommons.org/licenses/by/4.0/
), which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
License (CC BY;
https://creativecommons.org/licenses/by/4.0/
), which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Sponsor
National Institute for Health Research
Imperial College Healthcare NHS Trust - CLRN Funding
Imperial College Healthcare NHS Trust
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/28323997
PII: 3064424
Grant Number
RDA11 79560
RDC06 79560
RDC06 79560
Subjects
Endocrinology & Metabolism
07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
06 Biological Sciences
Publication Status
Published
Coverage Spatial
United States