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@article{Cuenco:2017:10.1210/en.2016-1827,
author = {Cuenco, J and Minnion, J and Tan, T and Scott, R and Germain, N and Ling, Y and Chen, R and Ghatei, M and Bloom, S},
doi = {10.1210/en.2016-1827},
journal = {Endocrinology},
pages = {1755--1765},
title = {Degradation paradigm of the Gut Hormone, Pancreatic Polypeptide, by hepatic and renal peptidases},
url = {http://dx.doi.org/10.1210/en.2016-1827},
volume = {158},
year = {2017}
}

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TY  - JOUR
AB  - 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.
AU  - Cuenco,J
AU  - Minnion,J
AU  - Tan,T
AU  - Scott,R
AU  - Germain,N
AU  - Ling,Y
AU  - Chen,R
AU  - Ghatei,M
AU  - Bloom,S
DO  - 10.1210/en.2016-1827
EP  - 1765
PY  - 2017///
SN  - 1945-7170
SP  - 1755
TI  - Degradation paradigm of the Gut Hormone, Pancreatic Polypeptide, by hepatic and renal peptidases
T2  - Endocrinology
UR  - http://dx.doi.org/10.1210/en.2016-1827
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28323997
UR  - http://hdl.handle.net/10044/1/45930
VL  - 158
ER  -

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Professor Sir Steve Bloom FMedSci, FRS

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