AB191. The roles of polyuria and hyperglycemia in bladder dysfunction in long-term diabetic rats

Aims of study: Diabetic bladder dysfunction (DBD), a collective description of clinical symptoms including decreased sensation, increased capacity, poor emptying, and also detrusor overactivity, is among the most common and costly complications of diabetes mellitus (DM). It is estimated that DBD occurs in approximately 87% of individuals diagnosed with DM, and substantially affects quality of life. Yet, little is known about the pathogenic mechanisms of DBD. Unlike other organs, the bladder experiences not only hyperglycemia, but also an increased volume of urine in DM. To aid in our knowledge of the pathophysiology of DBD and to aid development of specific treatments, identification of individual contributions of polyuria and hyperglycemia in the DBD is essential.

Materials and methods: Seventy two female Sprague-Dawley rats were divided into six groups: age-matched controls (control), sham urinary diversion (sham), urinary diversion (UD), streptozotocin-induced diabetics after sham urinary DM, streptozotocin-induced diabetics after urinary diversion (UD + DM), and 5% sucrose-induced diuretics after sham urinary diversion (DIU). UD was performed 10 days before diabetes induction by surgical disconnection of the ureters from the bladder and implantation to uterine cervix. Each group was subsequently evaluated 20 weeks after diabetes or diuresis induction. Twenty-four hour drinking and voided volumes were measured. Conscious cystometry (CMG) was examined. The bladders were harvested for histological examination and quantification of smooth muscle, urothelium, and collagen. The expressions of oxidative stress-related proteins, nitrotyrosine and manganese superoxide dismutase (MnSOD), in bladder were examined.

Results: Diabetes and diuresis caused increases in drinking volume, voided volume and bladder weight. The bladder weight decreased in the UD and UD + DM group. CMG showed increased inter-contractile intervals, voided volume and compliance in DIU and DM group, whereas decreased in the UD, and further in UD + DM group. The total tissue area, the tissue area of smooth muscle and urethelium increased in DIU and DM group, whereas decreased in UD and UD + DM group. As a percentage of the total cross sectional tissue area, collagen decreased in DIU and DM group, but increased in UD and UD + DM groups; smooth muscle and urothelium decreased in UD and UD + DM groups. The expression of nitrotyrosine and MnSOD increased in the DM and the UD + DM groups compared with other four groups.

Conclusions: Polyuria and hyperglycemia contribute differently in DBD. Polyuria induced significant bladder hypertrophy, whereas chronic hyperglycemia induces oxidative stress in bladder, which may play an important role in the later stage of DBD.

Keywords: Diabetic bladder dysfunction (DBD); polyuria; hyperglycemia; urinary diversion (UD)