Strict glucose control and elimination of NLRP3‐induced inflammation prevents diabetic bladder dysfunction in the female Akita mouse model

Abstract

AbstractPurposeDiabetic bladder dysfunction (DBD) is the most common diabetic complication. Logically, regulation of blood glucose should reverse dysfunction, but the Epidemiology of Diabetes Interventions and Complications study found strict control ineffective. However, it is possible that strict control may prevent DBD if initiated before symptoms appear. We examine the effect of early glucose control on development of DBD in the female diabetic Akita mouse (Type 1) and test the potential of inhibiting/deleting NLRP3 as adjunct therapy to glucose control.Materials and MethodsFemale Akita mice were bred NLRP3+/+ or NLRP3−/−. At 6 weeks of age, diabetics received either no glucose control or insulin pellets (s.c., Linshin) designed to poorly or strictly control blood glucose. At Week 15, blood glucose (glucometer), the extravasation potential of bladder (an indirect measurement of inflammation) and bladder function (urodynamics) were assessed.ResultsBlood glucose of diabetics was reduced in poorly controlled and strongly reduced in strictly controlled groups. Levels were not affected by deletion of NLRP3. Evans blue dye extravasation correlated with glucose control and was eliminated in the NLRP3−/− groups. Urodynamics found markers of overactivity in diabetics which was improved in the poorly controlled group and eliminated in the strictly controlled group. In the NLRP3−/− mice, no bladder dysfunction developed, regardless of glucose control.ConclusionsEarly‐initiated strict glycemic control and NLRP3 elimination can effectively prevent DBD, suggesting hyperglycemia acts through NLRP3‐induced inflammation to trigger DBD.