A systematic review of urinary bladder hypertrophy in experimental diabetes: Part 2. Comparison of animal models and functional consequences

Ellenbroek, Johanne H.; İnan, Ebru Arıoğlu; Michel, Martin C.

doi:10.1002/nau.23786

Cited by 31 publications

(58 citation statements)

References 102 publications

(500 reference statements)

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“…The cystometric test results clearly showed that the DM mice entered the compensated state at 6 weeks was characterized by sharply increased NVCs; subsequently, the decompensated state at 12 weeks was characterized by increased MBC, RV, and BC, and dramatically reduced MVP and VE, conforming to the previous studies . In addition, BWT, absolute and relative bladder weights of the DM mice persistently increased with the time, which are consistent with the increase in bladder capacity and prevised studies, thereby possibly reflecting a physical adaptation to an increased urine production and/or likely to induce an increased oxidative stress over time.…”

Section: Discussionsupporting

confidence: 86%

Time‐dependent functional, morphological, and molecular changes in diabetic bladder dysfunction in streptozotocin‐induced diabetic mice

Yuan

Wang

RuiWang

et al. 2019

Neurourology and Urodynamics

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AimDiabetic bladder dysfunction (DBD) is one of the most common and bothersome complications of diabetes mellitus (DM). This study aimed to investigate the functional, structural, and molecular changes of the bladder at 0, 3, 6, 9, and 12 weeks after DM induction by streptozotocin (STZ) in male C57BL/6 mice.MethodsMale C57BL/6J mice were injected with STZ (130 mg/kg). Then, diabetic general characteristics, cystometry test, histomorphometry, and contractile responses to α, β‐methylene ATP, KCl, electrical‐field stimulation, carbachol were performed at 0, 3, 6, 9, and 12 weeks after induction. Finally, protein and messenger RNA (mRNA) expressions of myosin Va and SLC17A9 were quantified.ResultsDM mice exhibited lower body weight, voiding efficiency and higher water intake, urine production, fasting blood glucose, oral glucose tolerance test, bladder wall thickness, maximum bladder capacity, residual volume, bladder compliance. In particular, nonvoiding contractions has increased more than five times at 6 weeks. And the amplitudes of spontaneous activity, contractile responses to all stimulus was about two times higher at 6 weeks but cut almost in half at 12 weeks. The protein and mRNA expressions of myosin Va and SLC17A9 were about two times higher at 6 weeks, but myosin Va was reverted nearly 40% while SLC17A9 is still higher at 12 weeks.ConclusionsDBD transitioned from a compensated state to a decompensated state in STZ‐induced DM mice at 9 to 12 weeks after DM induction. Our molecular data suggest that the transition may be closely related to the alterations of myosin Va and SLC17A9 expression levels in the bladder with time.

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Section: Discussionsupporting

confidence: 86%

Time‐dependent functional, morphological, and molecular changes in diabetic bladder dysfunction in streptozotocin‐induced diabetic mice

Yuan

Wang

RuiWang

et al. 2019

Neurourology and Urodynamics

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“…Since the 42-nd day of the experiment, the disorganization of the structure of BM appears, and on the 56-70-th day BM becomes lamellar. These changes of BM are associated with non-enzymatic glycosylation of its proteins, triggered and intensified by hyperglycemia during development of diabetes [8,9,45], and an increasing in level of glycosylated hemoglobin since the 14-th day till the end of the experiment indicates on this. We found considerable dystrophic changes in the endothelial cells at the ultrastructural level since the 42-nd day of diabetes; they increased until the end of the experiment, when the signs of their destruction appeared.…”

Section: Resultsmentioning

confidence: 99%

“…Diabetic microangiopathy with various manifestations and degrees of severity always develops during diabetes; it has a significant effect on the development of functional damage and reorganization of the structural components of various tissues and organs [2,3,5,6,8,11,14,15,16,17,21,22,28,29,34,43,45].…”

Section: Problem Statement and Analysis Of The Latest Researchmentioning

confidence: 99%

Reorganization of Intraorganic Blood Vessels of the Bladder in Experimental Diabetes Mellitus

et al. 2018

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Objective: To give histologic, morphometric and ultrastructural characteristics of intraorganic hemovessels of the urinary bladder of rats at the stages of streptozotocin diabetes. Material and methods. There were used 70 Wistar male rats; diabetes mellitus was modeled with streptozotocin (60 mg / kg of body weight); material was taken on 14, 28, 42, 56 and 70-th day of experiment; histological, morphometric and electron microscopic research was performed. Results The microscopic, morphometric and ultrastructural peculiarities of transformation of intraorganic blood vessels of rats’ bladder during streptozotocin diabetes were detected. Conclusions: 1) the bladder diabetic microangiopathy is nonspecific process, the specificity of which is determined by the degree of expressiveness of vascular disorders which are characterized by these: a) the change of arteriolar vascular tone manifesting itself initially by dilatation, then by decrease of the lumen, then by secondary expansion; b) reconstruction of hemocapillar basal membrane, which becomes thicker 3.22-fold by the end of the experiment, disorganized and lamellar; c) blood rheological disturbances expressed in sludges in particular venules on the 14th day of experiment, on the 28th – in most venules, on the 42nd – also in capillaries, on the 56-70-th generalized sludge syndrome of all bladder layers appears; 2) diabetic angiopathy is accompanied with swelling of different genesis: interstitial one increases till the 28th day of experiment, since the 42nd it decreases; since the 42nd day plasma percolation of perivascular connective tissue increases; swelling of endotheliocytes appears on the 28-42th day of diabetes.

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“…For instance, detrusor overactivity and non‐voiding contractions are the closest proxy parameter of urgency in animal models . They can be observed in a variety of animal models, including spontaneously hypertensive rats, rats with renovascular hypertension or congestive heart failure, mice with sickle cell disease, and various rodent models of type 1 and 2 diabetes . If patients presenting with OAB represent a group of underlying pathologies, it is unlikely that a single master switch exists.…”

Section: Hurdles To Drug Development In Oabmentioning

confidence: 99%

“…46 They can be observed in a variety of animal models, including spontaneously hypertensive rats, 47 rats with renovascular hypertension 48 or congestive heart failure, 49 mice with sickle cell disease, 50 and various rodent models of type 1 and 2 diabetes. 51 If patients presenting with OAB represent a group of underlying pathologies, it is unlikely that a single master switch exists. Accordingly, it is also unlikely that a single drug target is promising to make the vast majority of patients with OAB symptom-free.…”

Section: Hurdles To Drug Development In Oabmentioning

confidence: 99%

Where will the next generation of medical treatments for overactive bladder syndrome come from?

Michel

2020

Int J of Urology

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This review article discusses the medical need for improved medical treatments of overactive bladder syndrome, and the hurdles and research required to address that need. Currently, few overactive bladder syndrome patients stay on long‐term treatment, largely because efficacy expectations are not met, and tolerability is considered insufficient for the chronic treatment of a non‐life‐threatening condition. Therefore, a medical need exists for improved tolerability and, even more importantly, improved efficacy. It is unlikely that major improvements of efficacy and tolerability can be achieved within the currently approved drug classes. Work in experimental animals suggests that many causes of overactive bladder syndrome exist – each with a distinct pathophysiology. This makes it unlikely that a single medication can address the pathophysiology and treatment needs of all overactive bladder syndrome patients; accordingly, any medication will appear to have only moderate efficacy in the overall group of overactive bladder syndrome patients, even if it fully eliminates symptoms within a subset of patients. It is proposed that only identification of subsets of patients with a defined pathophysiology (and biomarkers thereof) will allow the development and use of targeted treatment that can be highly effective in such subsets.

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A systematic review of urinary bladder hypertrophy in experimental diabetes: Part 2. Comparison of animal models and functional consequences

Abstract: To better understand the relevance of bladder hypertrophy in many models of experimental diabetes, more studies in models of type 2 diabetes are urgently needed. Moreover, the role of factors other than hypertrophy in the genesis of bladder dysfunction requires further exploration.

Cited by 31 publications

References 102 publications

Time‐dependent functional, morphological, and molecular changes in diabetic bladder dysfunction in streptozotocin‐induced diabetic mice

Time‐dependent functional, morphological, and molecular changes in diabetic bladder dysfunction in streptozotocin‐induced diabetic mice

Reorganization of Intraorganic Blood Vessels of the Bladder in Experimental Diabetes Mellitus

Where will the next generation of medical treatments for overactive bladder syndrome come from?

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