Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Dissertation
Type II diabetes and detrusor muscle function: compensated and decompensated states
Doctor of Philosophy (Ph.D.), Drexel University
Jul 2016
DOI:
https://doi.org/10.17918/etd-7159
Abstract
Bladder smooth muscle (detrusor muscle) undergoes temporal changes in response to diabetes, resulting in diabetic bladder dysfunction (DBD). DBD induces a compensated state of bladder function exhibiting detrusor muscle remodeling and a hypercontractile phenotype progressing into a decompensated state of bladder function and a hypocontractile phenotype. While the majority of DBD studies have been performed in type I diabetes, there are relatively few in type II diabetes; in these studies none have characterized the two states of DBD. Our studies utilized a type II diabetic model induced by a high-fat diet, to induce insulin resistance, and low-dose streptozotocin (HFD/STZ), to induce hyperglycemia and compromised [beta]-cell function. The goal of this study was to investigate the timeline of DBD development, detrusor muscle contractility, and underlying mechanisms during the two states of DBD. The compensated state was characterized by increased volume per void, detrusor muscle hypertrophy, and increased contractility to carbachol and ATP. These results indicated that the enhanced contractility to carbachol was due to increased levels of M2 expression, without corresponding changes in myosin light chain (MLC) phosphorylation. The decompensated state was characterized by increased volume per void and number of voids, detrusor hypertrophy, and increased contractility to ATP but not carbachol. This suggested that progression of DBD involves decreased contractility to muscarinic stimulation. In addition, proteins involved with calcium sensitization and MLC demonstrated decreased phosphorylation levels. Decompensated detrusor also exhibited enhanced purinergic neurogenic force. The underlying increase in purinergic component of detrusor contractility is a possible therapeutic target for DBD.
Metrics
19 File views/ downloads
21 Record Views
Details
- Title
- Type II diabetes and detrusor muscle function
- Creators
- Nicole Siobhan Klee - DU
- Contributors
- Robert S. Moreland (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 7159; 991014632689904721