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Original Research
NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation
Francis M. Hughes, Jr., Nathan A. Hirshman, Brian M. Inouye, Huixia Jin, Eloise W. Stanton, Chloe E. Yun, Leah G. Davis, Jonathan C. Routh and J. Todd Purves
Diabetes 2018 Nov; db180845. https://doi.org/10.2337/db18-0845
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Abstract

The NLRP3 inflammasome senses diabetic metabolites and initiates inflammation implicated in diabetic complications and neurodegeneration. No studies have investigated NLRP3 in diabetic bladder dysfunction (DBD), despite a high clinical prevalence. In vitro, we found that numerous diabetic metabolites activate NLRP3 in primary urothelial cells. In vivo we demonstrate NLRP3 is activated in urothelia from a genetic Type 1 diabetic mouse (Akita) by week 15. We then bred a NLRP3-/- genotype into these mice and found this blocked bladder inflammation and cystometric markers of DBD. Analysis of bladder innervation established an NLRP3-dependent decrease in overall nerve density and Aδ-fibers in the bladder wall along with an increase in C-fiber populations in the urothelia, which potentially explains the decreased sense of bladder fullness reported by patients and overactivity detected early in DBD. Together, the results demonstrate the role of NLRP3 in the genesis of DBD and suggest specific NLRP3-mediated neuronal changes can produce specific DBD symptoms.

  • Received August 1, 2018.
  • Accepted November 5, 2018.
  • © 2018 by the American Diabetes Association.
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March 2019
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NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation
Francis M. Hughes, Nathan A. Hirshman, Brian M. Inouye, Huixia Jin, Eloise W. Stanton, Chloe E. Yun, Leah G. Davis, Jonathan C. Routh, J. Todd Purves
Diabetes Nov 2018, db180845; DOI: 10.2337/db18-0845

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NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation
Francis M. Hughes, Nathan A. Hirshman, Brian M. Inouye, Huixia Jin, Eloise W. Stanton, Chloe E. Yun, Leah G. Davis, Jonathan C. Routh, J. Todd Purves
Diabetes Nov 2018, db180845; DOI: 10.2337/db18-0845
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© 2019 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.