Exercise improves bladder function in diabetic mice

Acta Cirurgica Brasileira, 2008

2021

The urinary bladder is markedly enlarged in the type 1 diabetes mellitus model of streptozotocin (STZ)-injected rats, but much less data exist for models of type 2 diabetes (T2DM). Diabetic polyuria has been proposed to explain bladder enlargement. We have collected data on bladder weight and blood glucose from 16 studies representing 9 distinct rodent diabetes (7 T2DM) and obesity models; some included arms with diets and/or pharmacological treatments. Data were analyzed for bladder enlargement and for correlations between bladder weight on the one and glucose levels on the other hand. Our data confirm major bladder enlargements in STZ rats, minor if any enlargement in fructose-fed rats, db/db mice and mice on a high-fat diet. For the first time we report bladder weight data on 5 other models with presence and degree of bladder enlargement being heterogeneous across models. Bladder weight was correlated with plasma glucose in some but not other models, but correlations were moderat...

Korean Journal of Urology, 2006

We assessed whether urethral dysfunction related to nitric oxide (NO) is responsible for voiding dysfunction in rats with non-insulin dependent diabetes mellitus. Materials and Methods: A total of 27 male Sprague-Dawley rats (14 diabetic rats and 13 control rats) were included. Diabetes mellitus was induced by intraperitoneal administration of streptozotocin (90mg/kg) on the second day after birth. Cystometry with determining the detrusor leak point pressure (LPP) was performed in the diabetic and control rats at the age of 12 and 24 weeks. The effect of intravenous injection with Lnitro-arginine-methyl ester (L-NAME) as a NO inhibitor and sodium nitroprusside (SNP) as a NO donor were also evaluated. Results: Diabetic rats showed an increased bladder capacity and a higher detrusor LPP than the controls at both ages. After intravenous injection of L-NAME, the control rats showed an increased detrusor LPP, but no change was observed in the diabetic rats. With administering SNP, the detrusor LPP was decreased in both the diabetic and control rats. Conclusions: Urethral resistance was more increased in the diabetic rats than the controls, which may be the result of dysfunction of the urethral nerve containing NO. The urethral factor, in addition to cystopathy, also plays an important role for the pathogenesis of voiding dysfunction in diabetic patients. ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

International journal of health sciences

Aims: To clarify the effect of DM type 2 on bladder contractility in type 2 diabetic patients. Methods: Patients (60 adult male patients) with lower urinary tract symptoms (LUTS) underwent a detailed urodynamic investigation. Urodynamic findings were classified as diabetic cystopathy [DC, characterized by impaired bladder sensation, increased post-void residual urine (PVR) and increased bladder capacity and decreased bladder contractility], detrusor overactivity. Results: All the patients in the diabetic group had type 2 diabetes mellitus for average 14 years and only 9/60 patients(15% of the diabetic group) has weak detrusor contractility their BCI less than 100. The rest of diabetic group 51/60 (85%) had good detrusor contractility. This means that diabetes (even with long duration>10 years) does not affect the detrusor contractility in our diabetic patients. 30 patients of the group (50%) had increased cystometric capacity (>450 CC),12 patients (20%) had reduced cystometric...

Frontiers in Pharmacology, 2010

Diabetic cystopathy is a well-recognized complication of diabetes mellitus, which usually develops in middle-aged or elderly patients with long-standing and poorly controlled disease. It may have broad spectrum clinical presentations. Patients may be asymptomatic, or have a wide variety of voiding complaints from overactive bladder and urge incontinence to decreased bladder sensation and overflow incontinence. This review focuses on pathophysiological mechanisms responsible for urologic complications of diabetes and emphasizing on recent developments in our understanding of this condition. We also tried to shed some light on therapeutic modalities like behavioral, pharmacological, and surgical approaches.

Neurourology and urodynamics, 2018

To better understand the genesis and consequences of urinary bladder hypertrophy in animal models of diabetes. This part of a three-article series will analyze urinary bladder hypertrophy in the diabetes mellitus type 1 model of rats injected with streptozotocin (STZ). A systematic search for the key word combination "diabetes," "bladder" and "hypertrophy" was performed in PubMed; additional references were identified from reference lists of those publications. All papers were systematically extracted for relevant information. A total of 39 studies were identified that quantitatively reported on bladder hypertrophy in rats upon injection of STZ; of which several reported on multiple time points yielding a total of 83 group comparisons. Bladder hypertrophy was found consistently, being fully developed as early as 1 week after STZ injection (bladder weight 188 ± 59% of matched control). Hypertrophy was similar across sexes and STZ doses (35-40 vs 50-65 mg...

Frontiers in Physiology

The urinary bladder is markedly enlarged in the type 1 diabetes mellitus model of streptozotocin-injected rats, which may contribute to the frequent diabetic uropathy. Much less data exists for models of type 2 diabetes. Diabetic polyuria has been proposed as the pathophysiological mechanism behind bladder enlargement. Therefore, we explored such a relationship across nine distinct rodent models of diabetes including seven models of type 2 diabetes/obesity by collecting data on bladder weight and blood glucose from 16 studies with 2–8 arms each; some studies included arms with various diets and/or pharmacological treatments. Data were analysed for bladder enlargement and for correlations between bladder weight on the one and glucose levels on the other hand. Our data confirm major bladder enlargement in streptozotocin rats and minor if any enlargement in fructose-fed rats, db/db mice and mice on a high-fat diet; enlargement was present in some of five not reported previously models....

Frontiers in Pharmacology

Introduction: Diabetes often leads to lower urinary tract dysfunction. The most frequently assessed parameter of urinary bladder dysfunction in animal models of diabetes is an enlargement of the bladder, which is consistently observed in type 1 and less consistently in type 2 diabetes. The vast majority of studies on bladder weight in animal models of diabetes and obesity has been performed in males, and no studies have directly compared this outcome parameter between sexes.Methods: Therefore, we have compared bladder weight and bladder/body weight ratio in five mouse models of obesity and diabetes (RIP-LCMV, db/db, ob/ob (two studies), insulin receptor substrate 2 (IRS2) knock-out mice and mice on a high-fat diet; pre-specified secondary analysis of a previously reported study).Results: In a pooled analysis of the control groups of all studies, females exhibited slightly lower glucose levels, lower body weight, and lower bladder weight, but bladder/body weight ratio was similar in ...

The Journal of Urology, 2009

We studied urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in diabetic women. Materials and Methods: A total of 86 consecutive type 2 diabetic women with minimal confounders of voiding dysfunction followed at a diabetes clinic were prospectively enrolled and subjected to urodynamic studies. The sensory response of A␦ and C fibers of the bladder was measured by intravesical current perception threshold testing at frequencies of 250 and 5 Hz, respectively. Results: Of these 86 women 30 (34.9%) were classified as having detrusor underactivity, 12 (14.0%) presented signs of detrusor overactivity, 11 (12.8%) were referred to as having bladder outlet obstruction and 33 (38.4%) showed normal detrusor function on urodynamics. The normal detrusor function group was the reference group. The detrusor underactivity group showed impaired emptying function and decreased sensation on cystometry and intravesical current perception threshold testing. The detrusor overactivity group showed impaired storage and emptying function but had no significant changes in intravesical current perception threshold values. When the normal detrusor function group and detrusor underactivity group were pooled to perform multivariate analysis, an increase in current perception threshold values was associated with a decrease in bladder voiding efficiency on 5 and 250 Hz current perception threshold testing. Conclusions: Our data provide the electrophysiological evidence that indicates an association between impaired A␦ as well as C fiber bladder afferent pathways and poor emptying function in diabetic women with detrusor underactivity. Diabetes can affect the bladder presumably via peripheral pathogenetic mechanisms to induce detrusor overactivity with impaired contractility.

Frontiers in Physiology, 2020

Serum levels of estrogen decrease at climacterium and directly interfere with the urogenital tract. Urinary bladder (UB) is responsive to hormonal changes, especially estrogen. Resistance exercise elicits benefits on severe chronic diseases. Nevertheless, it is still unclear whether the resistance exercise directly affects the UB in ovariectomized (OVx) rats. This study focused on investigating the effects of resistance exercise on UB function and morphology in OVx and control rats. Adult female Wistar rats (∼250-300 g, 14-16 weeks old) [control (n = 20) and OVx (n = 20)] were divided in the following groups: sedentary (SED), and trained over 1 week (acute), 3 weeks (intermediate), and 10 weeks (chronic). Training was carried out in a ladder, with six bouts in alternate days with 75% of body weight load attached to the tail of the animal. Afterward, the animals were isoflurane anesthetized for evaluation of intravesical pressure (IP) changes upon topical administration of acetylcholine (Ach) and noradrenaline (NE) on the UB. At the end of the experiment, the UB was harvested for histological analysis and stained with hematoxylin-eosin and picrosirius red. Ach increased the IP in both OVx and control rats, whereas NE decreased the IP. However, the acute and intermediate groups showed attenuated responses to Ach and NE, while the chronic groups recovered the responses to Ach and NE close to those observed in SED groups. Acute and intermediate groups also showed decreased thickness of the muscular layer, with a reversal of the process with chronic training. In the OVx groups, the acute training reduced the thickness of the smooth muscle and mucosal layers, whereas chronic training increased it. Urothelium thickness decreased in the OVx SED and acute groups. Collagen type I fibers (CI-F) reduced in OVx SED acute and intermediate groups, while collagen type III fibers (CIII-F) increased in the OVx acute group. In the mucosal layer, the volume density of CFs reduced in OVx rats compared to control groups and chronic training resulted in their recovery. Our data suggest that chronic resistance exercise for 10 weeks reversed the functional and morphological changes caused by hypoestrogenism.

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2012

Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus (DM), is characterized by a broad spectrum of symptoms including urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late, it is important to understand the chronic impact of DM on bladder tissues. While changes in bladder smooth muscle and innervation have been reported in diabetic patients, the impact of DM on the specialized epithelial lining of the urinary bladder, the urothelium (UT), is largely unknown. Quantitative polymerase chain reaction analysis and electron microscopy were used to evaluate UT gene expression and cell morphology 3, 9, and 20 wk following streptozotocin (STZ) induction of DM in female Sprague-Dawley rats compared with age-matched control tissue. Desquamation of superficial (umbrella) cells was noted at 9 wk DM, indicating a possible breach in barrier function. One causative factor may be metabolic burden due to chronic hyperglycemia, suggested by upregu...

Journal of Urology, 2011

We studied bladder motor dysfunction and searched for markers of neurogenic and myogenic alterations among fructose fed rats with or without abnormal voiding behavior. Materials and Methods: Female Wistar rats were fed with a fructose rich diet (60%) or a normal diet for 6 months. Based on cystometry and voiding behavior the fructose fed rats were divided into 3 groups, including a group with normal detrusor function with normal micturition frequency, a group with detrusor overactivity with increased micturition frequency and a group with acontractile detrusor with increased micturition frequency. Denuded bladder tissues were obtained to assess in vitro detrusor contractility, postsynaptic receptors, smoothelin, nitrosative products and the intrinsic pathway of apoptosis. Results: Fructose fed rats with abnormal voiding behavior had obvious neurogenic and myogenic alterations, including increased expression of postsynaptic receptors, dysregulation of smoothelin and decreased expression of Bcl-2 with a subsequent increase in apoptotic cells in the bladder stroma, causing decreased carbachol induced contractility. Rats with detrusor overactivity were also insulted by nitrosative stress associated with nitrotyrosine up-regulation in the bladder tissue. Up-regulation of M 2 and M 3-muscarinic receptors, and P2X 1 receptors appeared to be generalized alterations of fructose fed rats and not exclusive to those with detrusor overactivity. Conclusions: Up-regulation of postsynaptic receptors and dysregulation of smoothelin contribute to overactive bladder symptoms in rats with metabolic syndrome. Nitrosative stress and decreased Bcl-2 expression lead to bladder muscle cell loss via the intrinsic pathway of apoptosis, which may further deteriorate bladder function.

Autonomic neuroscience : basic & clinical, 2014

Neuropathy and cystopathy are two common conditions in patients with chronic diabetes. Despite obvious bladder sensory and motor nerve dysfunction in diabetes, no studies have selectively explored whether sensory or motor innervation is affected in the bladder. In the present study, we tested the hypothesis that loss of bladder sensory and motor fibers is responsible for bladder sensory and motor dysfunction. Parasympathetic and sensory innervation of the bladder dome and neck were examined using immunohistochemistry (IHC) and stereology in adult female rats 12weeks after induction of diabetes by streptozotocin. Naïve and age matched rats were evaluated as controls. Diabetic rats had mean blood glucose level of >400mg/dl, and bladder weights and thicknesses that were more than doubled compared to naïve rats. In naïve rats, parasympathetic vesicular acetylcholine transporter (VAT) and sensory calcitonin gene-related peptide (CGRP) immunopositive nerve fibers were located in bladde...

Frontiers in Pharmacology, 2019

Hypertrophy and dysfunction of the urinary bladder are consistently observed in animal models of type 1 and less consistently in those of type 2 diabetes. We have tested the effects of mild hyperglycemia (n = 10 per group) in a randomized, blinded study and, in a blinded pilot study, of type 2 diabetes (n = 6 per group) and its treatment with dapagliflozin (1 mg/kg per day) on weight, contraction, and relaxation of the rat bladder. Based on a combination of high-fat diet and a low dose of streptozotocin, animals in the main study reached a mean peak blood glucose level of about 300 mg/dl, which declined to 205 mg/dl at study end. This was associated with a small, if any, increase in bladder weight. In a pooled analysis of all animals of the main and the pilot study, we detected a correlation of moderate strength between blood glucose and bladder weight (r 2 = 0.2013; P = 0.0003 for Pearson correlation coefficient). Neither the main nor the pilot study found evidence for an altered contractility (responses to carbachol or KCl) or relaxation (responses to isoprenaline, fenoterol, CL 316,243, or forskolin). Treatment with dapagliflozin in the absence of hyperglycemia increased diuresis in the main study by 43% relative to control and increased bladder weight by 15% in the pooled groups of both studies (post hoc analysis). We conclude that mild hyperglycemia has no major effects on bladder hypertrophy or function.

British Journal of Urology, 1984

The morphology of the rat bladder was studied following 8 weeks of streptozotocininduced diabetes, at which stage distension of the bladder had occurred. Evidence is presented for hypertrophy of the smooth muscle of the bladder wall in experimental diabetes. It is suggested that the morphological changes found in the diabetic rat bladder are associated with polyuria. The results are discussed in relation to clinical studies of bladder dysfunction in diabetes mellitus.