Diabetic bladder dysfunction progresses from an overactive to an underactive phenotype in a type-1 diabetic mouse...

Diabetic bladder dysfunction (DBD) is a prevalent diabetic complication thought to progress from overactive (OAB) to underactive (UAB) bladder. Previously we found OAB at 15 weeks in the Akita mouse, a genetic model of Type 1 diabetes. The first aim of this study assesses bladder function at 30 weeks to assess progression. In addition, inflammation triggered by the NLRP3 inflammasome is implicated in DBD. In a second aim we assessed a role for NLRP3 by crossing Akita mice with NLRP3^-/- mice.

Akita mice were bred with NLRP3^-/- mice. The effect of diabetes was assessed by comparing nondiabetic to diabetic mice (all NLRP3^+/+). The effect of diabetes in the absence of the NLRP3 inflammasome was assessed by comparing nondiabetic/NLRP3^-/- to diabetic/NLRP3^-/- mice. Mice were assessed at 30 weeks for blood glucose (glucometer), inflammation (Evans blue), bladder morphology (histology) and bladder function (urodynamics).

At 30 weeks blood glucose of nondiabetics and diabetics was not affected by the presence of absence of NLRP3. Diabetic/NLRP3^+/+ mice showed bladder inflammation and detrusor hypertrophy which was blocked in the diabetic/NLRP3^-/- mice, clearly showing a role for NLRP3. When bladder function was examined, diabetic/NLRP3^+/+ showed an increase in voiding volume and a decrease in frequency, two signs of underactive bladder. However, in the NLRP3^-/- mice, diabetes was unable to effectuate these changes, demonstrating that NLRP3-induced inflammation is responsible for UAB symptoms in these mice.

Akita diabetic mice progress from OAB to UAB. NLRP3 is a possible target to treat DBD.