Skip to main content

NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation.

Publication ,  Journal Article
Hughes, FM; Hirshman, NA; Inouye, BM; Jin, H; Stanton, EW; Yun, CE; Davis, LG; Routh, JC; Purves, JT
Published in: Diabetes
February 2019

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 an 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

February 2019

Volume

68

Issue

2

Start / End Page

430 / 440

Location

United States

Related Subject Headings

  • Urinary Bladder
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Mutant Strains
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Female
  • Endocrinology & Metabolism
  • Diabetes Mellitus, Type 1
  • Caspase 1
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hughes, F. M., Hirshman, N. A., Inouye, B. M., Jin, H., Stanton, E. W., Yun, C. E., … Purves, J. T. (2019). NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation. Diabetes, 68(2), 430–440. https://doi.org/10.2337/db18-0845
Hughes, Francis M., Nathan A. Hirshman, Brian M. Inouye, Huixia Jin, Eloise W. Stanton, Chloe E. Yun, Leah G. Davis, Jonathan C. Routh, and J Todd Purves. “NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation.Diabetes 68, no. 2 (February 2019): 430–40. https://doi.org/10.2337/db18-0845.
Hughes FM, Hirshman NA, Inouye BM, Jin H, Stanton EW, Yun CE, et al. NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation. Diabetes. 2019 Feb;68(2):430–40.
Hughes, Francis M., et al. “NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation.Diabetes, vol. 68, no. 2, Feb. 2019, pp. 430–40. Pubmed, doi:10.2337/db18-0845.
Hughes FM, Hirshman NA, Inouye BM, Jin H, Stanton EW, Yun CE, Davis LG, Routh JC, Purves JT. NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation. Diabetes. 2019 Feb;68(2):430–440.

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

February 2019

Volume

68

Issue

2

Start / End Page

430 / 440

Location

United States

Related Subject Headings

  • Urinary Bladder
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Mutant Strains
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Female
  • Endocrinology & Metabolism
  • Diabetes Mellitus, Type 1
  • Caspase 1