Anagliptin, a dipeptidyl peptidase‐4 inhibitor, improved bladder function and hemodynamics in rats with bilateral internal iliac artery ligation

Hotta, Yuji; Takahashi, Sena; Tokoro, Misato; Naiki‐Ito, Aya; Maeda, Kotomi; Kawata, Ryoya; Kataoka, Tomoya; Ohta, Yoshichika; Hamakawa, Takashi; Takahashi, Satoru; Yasui, Takahiro; Kimura, Kazunori

doi:10.1002/nau.24449

Cited by 5 publications

(6 citation statements)

References 25 publications

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“…Awake cystometry was performed as previously described 13‐15 . Briefly, under isoflurane anesthesia, the rats’ abdomen were incised along the midline to expose the bladders.…”

Section: Methodsmentioning

confidence: 99%

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Impairment of accessory nerves around major pelvic ganglion leading to overflow urinary incontinence in rats

Maeda

Hotta

Shibayama

et al. 2021

Neurourology and Urodynamics

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Aims: To investigate the relationship between lower urinary tract function and the accessory nerve (ACN) arising from the major pelvic ganglion (MPG). Methods: Ten-week-old male Wistar/ST rats were randomly divided into eight groups according to the type of treatment (sham or bilateral accessory nerve injury [BACNI]) and the duration of observation (3 days, 1 week, 2 weeks, or 4 weeks: Sham-3d, Sham-1w, Sham-2w, Sham-4w, BACNI-3d, BACNI-1w, BACNI-2ws, and BACNI-4w. BACNI was induced in the following manner: the ACN was crushed for 1 min (2 mm away from the MPG) using reverse-action tweezers. The same procedure was performed on both sides. On the last day of each observation period, the bladder function was measured by awake cystometry, and histological evaluation was performed. Results: All rats in the Sham groups micturated normally. In the BACNI-3d and BACNI-1w groups, all rats showed symptoms of overflow urinary incontinence (OUI). This OUI improved gradually over time. The bladder's size in the BACNI group was significantly larger than that in the Sham group (p < .01). In addition, fibrosis was observed in the subserosa of the bladder of rats in BACNI groups. Conclusion: The BACNI model rats exhibited OUI, suggesting that ACN is involved in the lower urinary tract function. It might be possible that ACN controls the function of either the bladder, the urethra, or both.

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“…Awake cystometry was performed as previously described 13‐15 . Briefly, under isoflurane anesthesia, the rats’ abdomen were incised along the midline to expose the bladders.…”

Section: Methodsmentioning

confidence: 99%

“…Awake cystometry was performed as previously described. [13][14][15] Briefly, under isoflurane anesthesia, the rats' abdomen were incised along the midline to expose the bladders. A polyethylene catheter (PE-50) was inserted into the bladder dome and secured with a 5-0 suture.…”

Section: Awake Cystometrymentioning

confidence: 99%

Impairment of accessory nerves around major pelvic ganglion leading to overflow urinary incontinence in rats

Maeda

Hotta

Shibayama

et al. 2021

Neurourology and Urodynamics

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“…After the neurological evaluation, all rats received cystometry according to methods described previously [21,22,23]. With inhalation anesthesia (4% isoflurane for induction and 1.5%–2.0% isoflurane for maintenance), the abdomens of the rats were opened through a midline incision, and the bladders were exposed.…”

Section: Methodsmentioning

confidence: 99%

Change in the bladder function of rats with focal cerebral infarction induced by photochemically-induced thrombosis

Ota

Kubota

Hotta

et al. 2021

Preprint

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The photochemically-induced thrombosis (photothrombosis) method can create focal cerebral infarcts anywhere in the relatively superficial layers of the cerebrum; it is easy to implement and minimally invasive. Taking advantage of this versatility, we aimed to establish a new rat model of urinary frequency with focal cerebral infarction, which was characterized by its simplicity, nonlethal nature, and high reproducibility. The prefrontal cortex and the anterior cingulate cortex, which are urinary centers, were targeted for focal cerebral infarction, and urinary parameters were measured by cystometrogram. Cystometric analysis indicated that micturition intervals significantly shortened in photothrombosis-treated rats compared with those in the sham operative group on Days 1 and 7 (P < 0.01), but prolonged after 14 days, with no difference between the two groups. Immunopathological evaluation showed an accumulation of activated microglia, followed by an increase in reactive astrocytes at the peri-infarct zone after photothrombotic stroke. Throughout this study, all postphotothrombosis rats showed cerebral infarction in the prefrontal cortex and anterior cingulate cortex; there were no cases of rats with fatal cerebral infarction. This model corresponded to the clinical presentation, in that the micturition status changed after stroke. In conclusion, this novel model combining nonlethality and high reproducibility may be a suitable model of urinary frequency after focal cerebral infarction.

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“…Chronic hypoperfusion due to atherosclerosis of pelvic arteries is considered as a cause of bladder dysfunction (Michel et al 2015a ; Thurmond et al 2016 ). One study explored effects of a 4-week treatment with the dipeptidyl-peptidase 4 inhibitor anagliptin and the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide in a preventive setting in a rat model of acute bilateral internal iliac artery ligation (Hotta et al 2020 ). Neither the ligation nor the treatments affected glucose levels or bladder weight.…”

Section: Effects Of Antidiabetic Treatments On Lutd In Diabetesmentioning

confidence: 99%

Established and emerging treatments for diabetes-associated lower urinary tract dysfunction

Erdogan

Liu

Arioglu‐Inan

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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Dysfunction of the lower urinary tract (LUT) including urinary bladder and urethra (and prostate in men) is one of the most frequent complications of diabetes and can manifest as overactive bladder, underactive bladder, urinary incontinence, and as aggravated symptoms of benign prostate hyperplasia. We have performed a selective literature search to review existing evidence on efficacy of classic medications for the treatment of LUT dysfunction in diabetic patients and animals, i.e., α1-adrenoceptor and muscarinic receptor antagonists, β3-adrenoceptor agonists, and phosphodiesterase type 5 inhibitors. Generally, these agents appear to have comparable efficacy in patients and/or animals with and without diabetes. We also review effects of antidiabetic medications on LUT function. Such studies have largely been performed in animal models. In the streptozotocin-induced models of type 1 diabetes, insulin can prevent and reverse alterations of morphology, function, and gene expression patterns in bladder and prostate. Typical medications for the treatment of type 2 diabetes have been studied less often, and the reported findings are not yet sufficient to derive robust conclusions. Thereafter, we review animal studies with emerging medications perhaps targeting diabetes-associated LUT dysfunction. Data with myoinositol, daidzein, and with compounds that target oxidative stress, inflammation, Rac1, nerve growth factor, angiotensin II receptor, serotonin receptor, adenosine receptor, and soluble guanylyl cyclase are not conclusive yet, but some hold promise as potential treatments. Finally, we review nonpharmacological interventions in diabetic bladder dysfunction. These approaches are relatively new and give promising results in preclinical studies. In conclusion, the insulin data in rodent models of type 1 diabetes suggest that diabetes-associated LUT function can be mostly or partially reversed. However, we propose that considerable additional experimental and clinical studies are needed to target diabetes itself or pathophysiological changes induced by chronic hyperglycemia for the treatment of diabetic uropathy.

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Anagliptin, a dipeptidyl peptidase‐4 inhibitor, improved bladder function and hemodynamics in rats with bilateral internal iliac artery ligation

Cited by 5 publications

References 25 publications

Impairment of accessory nerves around major pelvic ganglion leading to overflow urinary incontinence in rats

Impairment of accessory nerves around major pelvic ganglion leading to overflow urinary incontinence in rats

Change in the bladder function of rats with focal cerebral infarction induced by photochemically-induced thrombosis

Established and emerging treatments for diabetes-associated lower urinary tract dysfunction

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