Functional, Structural, and Neuronal Alterations in Urinary Bladder during Diabetes: Investigations of a Mouse Model

Abstract

Urinary bladder dysfunction is a common complication in diabetes, but the mechanisms involved are undefined and treatment options are limited. Murine models provide opportunities to utilize transgenic technologies for bladder research and here we investigate the functional, structural and neuronal aspects of the bladder in a mouse model of type-1 diabetes. Mice were injected with streptozotocin (150 mg/kg) or vehicle and studied at 5 weeks. Increases in blood glucose and total urine output were observed. In vitro cystometry showed a 2-fold increase in bladder capacity and compliance and decreased intravesical plateau pressure in diabetics versus controls. Bladder structure and composition were evaluated by digital imaging; region-specific changes included increased smooth muscle and urothelium and no change in collagen content. Alterations in cholinergic, adrenergic and nitric oxide-related functional responsiveness were also observed. The prevalence of cholinergic and adrenergic neuronal tracts was determined by immunohistochemistry: decreased vesicular acetylcholine transferase was observed in smooth muscle, whereas tyrosine hydroxylase was increased in the lamina propria, demonstrating a ‘neuronal remodeling’ shift toward pro-relaxant neuronal pathways. These studies demonstrate that this mouse model of diabetes exhibits important features of urinary bladder remodeling that are similar to the findings in humans and other animal models and will therefore be useful for further mechanistic investigations.

Urethral dysfunction due to alloxan-induced diabetes. Urodynamic and morphological evaluation

“…We also chose not to offer any treatment, including insulin replacement, to enhance the effects of the hyperglycemic state on the tissues we evaluated. In the present study, the efficacy of the alloxan-induced diabetic model was confirmed by the high levels of serum glucose and lower weights among the diabetic rats than among aging rats at their death [6][7][8][9][10][11][12][13] .…”

“…The evaluation was performed after intraperitoneal anesthesia with urethane (1.25 mg/kg weight) 6 . After suprapubic median laparotomy, a PF-50 polyethylene catheter was introduced and fixed on the bladder fundus and exteriorized by counter-opening in the dorsolateral region.…”

Glucose-Dependent Enhancement of Diabetic Bladder Contraction Is Associated with a Rho Kinase-Regulated Protein Kinase C Pathway

“…Assessment of bladder smooth muscle contractility is important in terms of understanding the mechanisms governing diabetic dysfunctions because of the involvement of neuronal dysfunction in diabetes (Poladia and Bauer, 2005). Alterations of contractile responses have been documented,…”

“…Although this condition is not life-threatening, it is associated with several debilitating symptoms, which disrupt patient quality of life. However, therapy for diabetic bladder dysfunctions has not been established.Assessment of bladder smooth muscle contractility is important in terms of understanding the mechanisms governing diabetic dysfunctions because of the involvement of neuronal dysfunction in diabetes (Poladia and Bauer, 2005). Alterations of contractile responses have been documented,…”

“…Assessment of bladder smooth muscle contractility is important in terms of understanding the mechanisms governing diabetic dysfunctions because of the involvement of neuronal dysfunction in diabetes (Poladia and Bauer, 2005). Alterations of contractile responses have been documented, and correlations between receptor activity and/or intracellular signaling pathways have been suggested in various types of smooth muscle tissues isolated from diabetic models (Arun et al, 2005;Schulingkamp et al, 2005;Ma et al, 2008).…”