Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes

Abstract

Purpose: Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats.

Materials and methods: A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder.

Results: Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes.

Conclusions: Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction.

Figure 1

Representive tracings of conscious cystometrogram (CMG) from control, sham, DIU, DM, UD, and UD + DM rats 20 wk after DM or diuresis induction (from top to bottom). The infusion rate is 5 ml/hr for control, sham, UD, and UD + DM rats; 10 ml/hr for DIU and DM rats. Abbreviations: DIU, 5% sucrose-induced diuretics after sham urinary diversion; DM, diabetes mellitus; UD, urinary diversion.

Figure 2

Representative images of Masson’s trichrome staining of equatorial sections of urinary bladders from control, sham, DIU, DM, UD, and UD + DM rats 20 wk after DM or diuresis induction, showing smooth muscle (outer magenta), collagen (blue), and urothelium (inner light magenta). Scale bar, 500 µm. Abbreviations: DIU, 5% sucrose-induced diuretics after sham urinary diversion; DM, diabetes mellitus; UD, urinary diversion.

Figure 3

Representative immunoblotting results and quantitative analysis of nitrotyrosine (A, B) and MnSOD (C, D) levels in the bladder in control, sham, DIU, DM, UD and UD + DM rats 20 wk after DM or diuresis induction (n=4 per group). Each lane was from a single rat. Quantitative data are presented as mean plus standard error of the mean. Asterisks indicate significant differences compared with the value of control, sham, DIU and UD groups (P<0.05). Abbreviations: DIU, 5% sucrose-induced diuretics after sham urinary diversion; DM, diabetes mellitus; UD, urinary diversion.