Pharmacological Properties, Functional Alterations and Gene Expression of Muscarinic Receptors in Young and Old Type 2 Goto-Kakizaki Diabetic Rat Bladders

Saito, Motoaki; Okada, Shinichi; Kazuyama, Emi; Satoh, Itaru; Kinoshita, Yukako; Satoh, Keisuke

doi:10.1016/j.juro.2008.08.002

Cited by 22 publications

(36 citation statements)

References 18 publications

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“…Similar findings have been made in other male type II diabetic animal models, the SDT rat (32) and the db/db mouse (47), although the type II diabetic Goto-Kakizaki (GK) rat did not show increased void volume or frequency even at 70 wk of age (40). Bladder dysfunction tends to progress from a state of bladder compensation to decompensation, when decreased bladder contractility results in increased residual urine volumes (15).…”

Section: Discussionsupporting

confidence: 76%

“…While enhanced contractility to muscarinic agonists has been shown in many type II diabetic models (15,26,35,40,50), others have shown decreased contractility (30,43). There may be many explanations for the differences seen in these studies (species, diabetes induction methodology, and animal age), but it is interesting to note that both studies showing decreased contractility to muscarinic agonists were performed in animals with a longer duration of diabetes.…”

Section: Discussionmentioning

confidence: 96%

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Effect of type II diabetes on male rat bladder contractility

Kendig

Ets

Moreland

2016

American Journal of Physiology-Renal Physiology

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Kendig DM, Ets HK, Moreland RS. Effect of type II diabetes on male rat bladder contractility. Am J Physiol Renal Physiol 310: F909 -F922, 2016. First published January 28, 2016 doi:10.1152/ajprenal.00511.2015.-Type II diabetes is the most prevalent form of diabetes. One of the primary complications of diabetes that significantly affects quality of life is bladder dysfunction. Many studies on diabetic bladder dysfunction have been performed in models of type I diabetes; however, few have been performed in animal models of type II diabetes. Using the Zucker Diabetic Fatty (ZDF) rat model of type II diabetes, we examined the contractility and sensitivity of bladder smooth muscle in response to mediators of depolarization-induced contraction, muscarinic receptor-mediated contraction, ATP-induced contraction, and neurogenic contraction. Studies were performed at 16 and 27 wk of age to monitor the progression of diabetic bladder dysfunction. Voiding behavior was also quantified. The entire bladder walls of diabetic rats were hypertrophied compared with that of control rats. Contractility and sensitivity to carbachol and ATP were increased at 27 wk in bladder smooth muscle strips from diabetic rats, suggesting a compensated state of diabetic bladder dysfunction. Purinergic signaling was increased in response to exogenous ATP in bladders from diabetic animals; however, the purinergic component of neurogenic contractions was decreased. The purinergic component of neurogenic contraction was reduced by P2X receptor desensitization, but was unchanged by P2X receptor inhibition in diabetic rats. Residual and tetrodotoxin-resistant components of neurogenic contraction were increased in bladder strips from diabetic animals. Overall, our results suggest that in the male ZDF rat model, the bladder reaches the compensated stage of function by 27 wk and has increased responsiveness to ATP. diabetic bladder dysfunction; Zucker diabetic fatty rat; muscarinic receptors; purinergic receptors; electrical field stimulation DIABETES MELLITUS (DM) IS a disorder of carbohydrate metabolism typically characterized by defective insulin secretion or insulin resistance and subsequent hyperglycemia. In the past few decades, the prevalence of DM has been on the rise (1, 33), and lower urinary tract symptoms (LUTS) are among the most common complications of diabetes affecting up to 80% of patients (14). The most common and bothersome LUTS in diabetes is bladder dysfunction, with over 50% of diabetic patients experiencing some form of bladder dysfunction (48). The primary classic symptom diabetic patients exhibit is increased residual urine volume after voiding (23). More recent research suggests a combination of both storage and voiding problems (14). Experimental evidence now suggests a temporal profile of the development of diabetic bladder dysfunction (15). There is a progression from the compensated state, during which the bladder undergoes hypertrophy and the muscle becomes hypercontractile, to the decompensated state, when the muscle is hyp...

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 96%

Effect of type II diabetes on male rat bladder contractility

Kendig

Ets

Moreland

2016

American Journal of Physiology-Renal Physiology

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“…While ED has been previously reported in 10-and 18-wkold GK rats (12), previous studies investigating DBD in GK rats did not evidence major in vivo functional modifications in terms of voiding behavior or urodynamic alterations at 10 wk of age (43). Conversely, Aizawa et al (3) reported bladder underactivity in 46-wk-old GK rats and an increase in urine residual volume was evidenced in 70-wk-old GK rat (43).…”

mentioning

confidence: 86%

Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat

Oger-Roussel

Behr‐Roussel

Caisey

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Despite the fact that urogenito-sexual complications significantly impact the quality of life of diabetic patients, a robust in vivo experimental model is lacking. Bladder and erectile function in the Type 2 diabetic Goto-Kakizaki (GK) rat and responses to standard-of-care treatments for each disorder have been assessed. GK rats (n = 25, 18-wk-old, GK/Par colony) and age-matched Wistar rats (n = 23), characterized for their metabolic parameters, were used. Bladder function was assessed by cystometry in conscious rats treated by intravenous solifenacin (1 mg/kg). Subsequently, erectile function was assessed under anesthesia following electrical stimulation of the cavernous nerve in presence of intravenous sildenafil (0.3 mg/kg). GK rats displayed detrusor overactivity with a significant increase in frequency/amplitude of nonvoiding contractions during the filling phase, together with an increase in bladder capacity, intercontraction interval, voided volume, and maximal pressure of voiding contraction. Solifenacin significantly decreased parameters characterizing voiding contractions without modifying voiding efficiency. Erectile function in GK rats was markedly impaired and remained so after sildenafil treatment despite a significant improvement. GK rats display both bladder and erectile dysfunctions and respond at least partially to standard-of-care treatments for each disorder, thus representing a suitable model to investigate the pathophysiology and assess the efficacy of new therapeutic agents for Type 2 diabetes-associated bladder and erectile complications.

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“…With the predominance of urgency, frequency, and nocturia, the use of antimuscarinic medications may be beneficial in this population. Increased muscarinic receptor expression has been seen in streptozotocin-induced rat models, and this provides supporting evidence for the use of antimuscarinic medication to alleviate voiding symptoms in diabetic patients [16]. However, clinical data to support its use is scarce.…”

Section: Medical Managementmentioning

confidence: 97%

“…Increased responsiveness of these bladder strips to externally applied muscarinic agonists as well as increased muscarinic receptor density has been shown by some, while others have shown a decrease or no change in the muscarinic component [16]. Increased responsiveness to electrical field stimulation has been repeatedly seen and theorized to be secondary to changes in membrane composition, increased neurotransmitter release, increased calcium channel activity, and increased calcium sensitivity [17].…”

Section: Detrusor Smooth Muscle Dysfunctionmentioning

confidence: 99%

Bladder Dysfunction in Patients with Diabetes

2011

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With diabetes mellitus (DM) reaching epidemic proportions, the identification of voiding dysfunction as a common and burdensome complication of this disease is critical. Research into diabetic voiding dysfunction significantly lags behind other complications of DM, such as retinopathy and nephropathy. Recent studies have revealed that DM predisposes patients to a wide range of lower urinary tract dysfunction, from the classic diabetic cystopathy of incomplete emptying to urgency incontinence. In this review, we discuss the current concepts of diabetic voiding dysfunction with a critical analysis of the available evidence.

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Pharmacological Properties, Functional Alterations and Gene Expression of Muscarinic Receptors in Young and Old Type 2 Goto-Kakizaki Diabetic Rat Bladders

Abstract: Our data indicate that noninsulin dependent diabetes induces alterations in the muscarinic receptor system, which may contribute to the development of diabetic cystopathy.

Cited by 22 publications

References 18 publications

Effect of type II diabetes on male rat bladder contractility

Effect of type II diabetes on male rat bladder contractility

Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat

Bladder Dysfunction in Patients with Diabetes

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