Urothelial Dysfunction and Chronic Inflammation in Diabetic Patients with Overactive Bladder

Wang, Chung‐Cheng; Kuo, Hann‐Chorng

doi:10.1111/luts.12126

Cited by 24 publications

(19 citation statements)

References 22 publications

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“… 16 , 17 , 35 However, little attention has been focused on the bladder, with only a single recent study drawing a correlation between inflammation, urothelial dysfunction, and diabetes in patients. 18 To our knowledge, this is the first study to directly address bladder inflammation in an animal model of diabetes, and we found direct evidence that the bladder is indeed inflamed.…”

Section: Discussionmentioning

confidence: 60%

“… 13 – 15 While for many years there has been general evidence that inflammation plays an important role in the development of several diabetic complications, 16 , 17 there has been little evidence that it is occurring in the bladder. Suggestive indications were provided when Wang and Kuo 18 recently found that mast cells in the urothelium and suburothelial layer were increased in diabetic patients. In this study, we have examined the presence of inflammation in the bladder of the Akita diabetic mice at a time where they demonstrate DBD symptoms.…”

Section: Introductionmentioning

confidence: 99%

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Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria

Inouye¹,

Hughes²,

Jin³

et al. 2018

RRU

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PurposeDiabetes is a grave and progressive condition characterized by debilitating complications. Diabetic bladder dysfunction (DBD) is a very common complication with no specific treatments currently available. Unlike other tissues affected by this disease, the bladder is subjected to two independent insults; 1) polyuria, created by the osmotic effects of glucose in the urine, and 2) hyperglycemia itself. Based on our understanding of inflammation as a major contributor to the underlying organ damage in several other diabetic complications, its presence in the bladder during DBD and the contribution of polyuria and hyperglycemia to its development were assessed.MethodsAwake, restrained cystometry was performed on wild type C57BL/6 mice and diabetic (Akita) mice on a C57BL/6 background at 15 weeks of age. A subgroup of the Akita mice were treated with phlorizin, an inhibitor of sodium-glucose linked transporter types 1 and 2 that prevents glucose reabsorption in the kidney. All groups were assessed for serum glucose, 4-hour voiding totals, and inflammation in the bladder (Evans blue assay).ResultsAkita mice develop cystometrically-defined DBD by 15 weeks of age, as evidenced by an increase in urinary frequency, a decrease in voiding volume, and an increase in post-voiding residual volume. Phlorizin effectively normalized serum glucose in these animals while increasing the urine output. Inflammation in the bladder was present in the diabetic animals at this time point, but not detectable in animals receiving phlorizin.ConclusionInflammation in the bladder of diabetic mice correlates with the development of DBD and is triggered by hyperglycemia, not polyuria.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria

Inouye¹,

Hughes²,

Jin³

et al. 2018

RRU

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“…Previous reports have demonstrated that OAB may be caused by chronic inflammation (51,52) and proteins related with inflammation can be served as biomarker for OAB syndrome (53). In addition, modulating inflammatory response with anti-inflammation drugs can improve the detrusor contraction disorder (54,55).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Park

Lim

Kim

et al. 2018

Molecular & Cellular Proteomics

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SummaryOveractive bladder (OAB) syndrome is a condition that has four symptoms: urgency, urinary frequency, nocturia, and urge incontinence and negatively affects a patient's life. Recently, it is considered that the urinary bladder urothelium is closely linked to pathogenesis of OAB. However, the mechanisms of pathogenesis of OAB at the molecular level remain poorly understood, mainly as a result of lack of modern molecular analysis. The goal of this study is to identify a potential target protein that could act as a predictive factor for effective diagnosis and aid in the development of therapeutic strategies for the treatment of OAB syndrome. We produced OAB in a rat model and performed the first proteomic analysis on the mucosal layer (urothelium) of the bladders of sham control and OAB rats. The resulting data revealed the differential expression of 355 proteins in the bladder urothelium of OAB rats compared to sham subjects. Signaling pathway analysis revealed that the differentially expressed proteins were mainly involved in the inflammatory response and apoptosis.Our findings suggest a new target for accurate diagnosis of OAB that can provide essential information for the development of drug treatment strategies as well as establish criteria for screening patients in the clinical environment.

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“…[44] These animal and clinical studies of BoNT-A strengthen the evidence of its therapeutic effects in diabetic patients with OAB. Since muscarinic M3 and P2X3 protein expressions in the bladders of DM-associated OAB patients were significantly higher than those in the controls, BoNT-A detrusor injection may provide an alternative treatment for these patients [23].…”

Section: Inhibition Of Chronic Inflammation and Hypersensitivity By Imentioning

confidence: 96%

“…The findings of the animal studies have been further corroborated by a human study. Bladder mucosa was biopsied from 19 DM-associated OAB patients, 14 OAB patients without DM, and 10 healthy controls [23]. Decreased expression of urothelial junction protein (E-cadherin and ZO-1) and increased urothelial inflammation (mast cells) were noted in the non-diabetic OAB and diabetic OAB patients.…”

Section: Pathophysiology Of Dm-associated Oabmentioning

confidence: 99%

The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A

Wang

Jiang

Kuo

2020

Toxins

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Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely “botulinum toxin A” (BoNT-A) and “overactive bladder”, with or without the additional keywords “detrusor overactivity”, “diabetes mellitus”, “inflammation”, and “urodynamic study”. We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy.

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Urothelial Dysfunction and Chronic Inflammation in Diabetic Patients with Overactive Bladder

Abstract: Urothelial dysfunction and chronic suburothelial inflammation may contribute to the pathogeneses of OAB. However, DM does not aggravate the severity of urothelial inflammation in OAB patients.

Cited by 24 publications

References 22 publications

Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria

Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

The Pharmacological Mechanism of Diabetes Mellitus-Associated Overactive Bladder and Its Treatment with Botulinum Toxin A

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