Effect of type II diabetes on male rat bladder contractility

Abstract

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...

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

“…Among these, ZDF rats and db/db mice exhibit a comparable degree of blood glucose elevation as STZ‐injected rats, whereas Goto‐Kakizaki rats and Abyssinian‐Hartley guinea pigs have a much less severe diabetes (Figure , Supplemental Table S1). Although blood glucose was already markedly elevated in 16‐week old ZDF rats, micturition frequency was increased only moderately whereas voided volume was markedly reduced; despite similar glucose levels in 27‐week old animals, these exhibited a marked increase in both micturition frequency and voided volume . db/db mice also exhibited a considerable increase in micturition frequency but data on voided volume have unfortunately not been reported.…”

“…mRNA expression of subunits of L‐type Ca 2+ ‐channels was unchanged, whereas gene expression of some subunits of T‐type channels was increased, which could explain the greater inhibition by mibefradil. In ZDF rats, inconsistent changes of contractile responses were found 16‐week old animals; contractile responses were increased for ATP (but not muscarinic agonists or KCl) at 27 weeks but the latter could not be explained by changes in P2X 1 receptor mRNA expression . Thus, T2DM models with high glucose levels were inconsistent across models for changes in contractility, but too few studies have been reported for robust conclusions.…”

Administration of human umbilical cord blood mononuclear cells restores bladder dysfunction in streptozotocin‐induced diabetic rats

“…In another study, maximum contractile responses to carbachol were similar in bladders of type 2 diabetic (T2D) and normal rats . However, at 16 and 27 weeks of diabetes, the contractile response to carbachol was increased in detrusor smooth muscle, indicating a compensated state of diabetic bladder dysfunction . Although increased contractility to muscarinic agonists has been demonstrated in many models of T2D, other studies have reported decreased contractility .…”

“…Most patients with diabetes present bladder dysfunction, including overactive bladder, urinary urgency, frequency, incontinence, and impaired bladder contractility, as well as diminished quality of life . The connection between diabetes and urinary bladder is largely unknown, and several pharmacological and surgical interventions have been shown to be ineffective therapy for diabetic bladder dysfunction…”

“…Most patients with diabetes present bladder dysfunction, including overactive bladder, urinary urgency, frequency, incontinence, and impaired bladder contractility, as well as diminished quality of life. [1][2][3] The connection between diabetes and urinary bladder is largely unknown, and several pharmacological and surgical interventions have been shown to be ineffective therapy for diabetic bladder dysfunction. 4 In diabetes-induced tissue damage, stem cells give rise to specialized new functional cells by multilineage differentiation and selfrenewal, 5,6 as well as inducing paracrine effects through the release of bioactive components in the wound area.…”