Male Akita diabetic mice develop underactive bladder independent of NLRP3 that can be prevented with blood glucose control

Abstract

Aim:: Diabetic bladder dysfunction (DBD) is the most common diabetic complication. Patients present with overactive symptoms, underactive symptoms, or both. While strict glucose control may be expected to reverse DBD, prior studies have not been supportive. However, we hypothesize that strict control, soon after hyperglycemia appears, can prevent DBD development. Moreover, 50% of adult diabetics are poorly-controlled and it is unknown how this effects development of DBD. Thus, we investigated the effect of early glucose control (poor and strict) on DBD in male Akita diabetic mice (type 1). NLRP3-induced inflammation is critical to development of DBD in female Akita. Therefore, we also hypothesized that targeting NLRP3 may control or prevent DBD in male Akita, especially in a poorly-controlled population. Methods:: Akita mice (±NLRP3) were stratified into uncontrolled, poorly-controlled and strictly-controlled diabetic groups using insulin treatment (0, 0.125 or 0.25 U/day). Mice were assessed at 15 weeks for blood glucose, HbA1c, Evans blue dye extravasation (a marker of capillary permeability/inflammation) and bladder function. Results:: Blood glucose was elevated in diabetics, reduced in an insulin dose-dependent manner, and not affected by NLRP3 deletion. HbA1c levels followed a similar course but were more sensitive to insulin levels. Evans blue dye extravasation was prevented with glucose control and absent in NLRP3−/−mice. Diabetics exhibited signs of underactive bladder (increased void volume, decreased frequency) that was attenuated in the uncontrolled group but absent in the well-controlled group. Deleting NLRP3 did not affect voiding function. Conclusion:: Male Akita mice develop an underactive-like bladder, independent of NLRP3, which can be prevented with glucose control.

Keywords

• Bladder
• Diabetes
• Complications
• Inflammation
• Urodynamics