Podium Session

Poster, Podium & Video Sessions

PD12-06: Inflammasome Activation Early in the Development of Diabetic Bladder Dysfunction

Friday, May 12
4:20 PM - 4:30 PM
Location: BCEC: Room 159

Presentation Authors: Brian Inouye*, Francis M Hughes, Robin Lütolf, Clay Rouse, Wen-Chi Foo, J Todd Purves, Durham, NC

Introduction: The NLRP3 inflammasome has gained recognition for its role in mediating inflammation through its activation of pro-inflammatory cytokines like IL-1β. It has been implicated in diabetic sequelae such as nephropathy, retinopathy, neuropathy, and vasculopathy, and in sterile cystopathy such as hemorrhagic cystitis and bladder outlet obstruction. We hypothesize that the NLRP3 inflammasome is activated in the inflammatory response in diabetic bladder dysfunction (DBD), the most common of all diabetic complications.

Methods: Ins2 (Akita) diabetic mice and age-matched controls underwent 4hr voiding assays to determine development of early DBD, defined as increased frequency and smaller voided volumes. Inflammation and fibrosis were compared through bladder weights, Evans Blue assay, Masson&[prime]s trichrome stain, and H&E stain. Active caspase-1, a functional moiety of activated inflammasome, was targeted intracellularly by a fluorescent caspase inhibitor and measured through flow cytometry. Paired geometric mean fluorescence intensity was compared via paired T-test, and all other univariate analysis was performed with ANOVA. Significance was defined as p<.05.

Results: Diabetic mice demonstrated DBD as early as week 11 with increased frequency of voids (p<.01), increased total voided volume (p<.05), and decreased volume per void (p<.05), compared to wild type mice. Inflammasome activation was evident as witnessed by increased active caspase-1 in diabetic mice (Figure 1). Diabetic mice also had increased Evans blue extravasation, indicating increased capillary permeability, an early sign of inflammation. Furthermore, diabetic bladders demonstrated hypertrophy compared to wild type bladders (20.6 vs 18.9mg; p=0.2); however, there was no increase in collagen deposition or histological changes on H&E staining.

Conclusions: Inflammasomes are activated early in the development of diabetic bladder dysfunction and may contribute to the onset of voiding dysfunction.

Source Of Funding: 2017 Urology Care Foundation Residency Research Award sponsored by the Russell Scott, Jr, MD Research Fund; Intramural Funds provided by the Division of Urology, Department of Surgery of the Duke University School of Medicine

Brian M. Inouye, MD

Duke University

Brian M Inouye, MD is a urology resident at Duke University. He was awarded a 2016 Urology Care Foundation Resident Research Award for his proposed project, "The Mechanism of Inflammation in Diabetic Bladder Dysfunction." His current research focuses on the role of the NLRP3 inflammasome in acute diabetic bladder function with its presentation of irritative voiding symptoms.

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