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Anagliptin, a dipeptidyl peptidase‐4 inhibitor, improved bladder function and hemodynamics in rats with bilateral internal iliac artery ligation
Author(s) -
Hotta Yuji,
Takahashi Sena,
Tokoro Misato,
NaikiIto Aya,
Maeda Kotomi,
Kawata Ryoya,
Kataoka Tomoya,
Ota Yuya,
Hamakawa Takashi,
Takahashi Satoru,
Yasui Takahiro,
Kimura Kazunori
Publication year - 2020
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.24449
Subject(s) - medicine , dipeptidyl peptidase 4 , agonist , liraglutide , ligation , dipeptidyl peptidase , endocrinology , urology , receptor , type 2 diabetes , diabetes mellitus , biochemistry , chemistry , enzyme
Aims To investigate the effect of anagliptin (Ana), a dipeptidyl peptidase‐4 (DPP‐4) inhibitor, on acute ischemia‐induced bladder dysfunction in rats. Methods Eight‐week‐old female Wistar‐ST rats were randomly assigned into four groups: (a) sham; (b) ligation (Lig); (c) Lig + Ana; and (d) Lig + Liraglutide (a glucagon‐like peptide‐1 [GLP‐1] receptor agonist; Lira). Rats in the Lig, Lig + Ana, and Lig + Lira groups underwent ligature of the bilateral internal iliac arteries. Ana was orally administered mixed with the CE‐2 diet. Lira was subcutaneously administered once a day. Blood glucose levels, plasma dipeptidyl peptidase 4 (DPP‐4) activity, GLP‐1 levels, and bladder function were measured in all groups. Bladder blood flow was measured in the sham, Lig, and Lig + Ana groups, 4 weeks postsurgery. Results No differences in blood glucose levels among the groups were observed. DPP‐4 activity decreased in the Lig + Ana group ( P < .01). GLP‐1 levels in the Lig + Ana and Lig + Lira groups were higher than those in the sham and Lig groups ( P < .01). Intercontraction intervals (ICIs) were longer in the Lig and Lig + Lira groups than in the sham group ( P < .05), but similar to those observed in the Lig + Ana and sham groups. The Lig group exhibited reduced bladder blood flow relative to the sham group ( P < .01); however, this measure improved in the Lig + Ana group ( P < .01). Conclusions Ana administration improved ICIs and bladder blood flow after acute bladder ischemia through a GLP‐1 receptor‐independent signaling pathway, without altering the blood glucose levels. Therefore, Ana dosing might be useful to prevent ischemia‐induced bladder dysfunctions.