Diabetic bladder dysfunction progresses from an overactive to an underactive phenotype in a type-1 diabetic mouse model (Akita female mouse) and is dependent on NLRP3
| Autor: | Francis M. Hughes, Armand Allkanjari, Michael R. Odom, Huixia Jin, J. Todd Purves |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Blood Glucose
Inflammation Male Inflammasomes Urinary Bladder Overactive Urinary Bladder General Medicine General Biochemistry Genetics and Molecular Biology Article Diabetes Mellitus Experimental Disease Models Animal Mice Diabetes Mellitus Type 1 Phenotype NLR Family Pyrin Domain-Containing 3 Protein Animals Humans Female General Pharmacology Toxicology and Pharmaceutics |
| Zdroj: | Life Sci |
| ISSN: | 1879-0631 |
| Popis: | AIMS: 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. MAIN METHODS: 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). KEY FINDINGS: 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 SIGNIFICANCE: Akita diabetic mice progress from OAB to UAB. NLRP3 is a possible target to treat DBD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect