Functional, Morphologic, and Molecular Biological Changes in the Bladder of OLETF Diabetic Rats according to Duration of Diabetes Mellitus

ABSTRACT

PURPOSE: Our study was undertaken to investigate changes in the bladder according to duration of diabetes mellitus in the Otsuka Long Evans Tokushima Fatty (OLETF) rat model, which is similar to type 2 diabetes. MATERIALS AND METHODS: OLETF rats (n=14) and Long Evans Tokushima Otsuka (LETO, n=14) rats were used. LETO is a normal control of OLETF. The animals were assigned to 4 groups L-40 group, LETO rats 40 weeks after birth (n=7); O-40 group, OLETF rats 40 weeks after birth (n=7); L-60 group, LETO rats 60 weeks after birth (n=7); and O-60 group, OLETF rats 60 weeks after birth (n=7). At 40 weeks or 60 weeks after birth, blood glucose, cystometry, bladder weight, detrusor contractility, and mRNA expression of nerve growth factor (NGF) were assessed. RESULTS: Cystometry showed that diabetic bladders had increased compliance compared with the control groups at 40 and 60 weeks, and the O-60 group had greater compliance than the O-40 group. Contractile responses to electrical stimulation, bethanecol (250microM), and ATP (10 mM) were decreased in the experimental groups compared with the control groups at 40 and 60 weeks, and the O-60 group had a lower contractile response than the O-40 group. The mRNA expression of NGF was decreased in the experimental groups compared with the control groups, and the O-60 group had lower expression than the O-40 group. Changes in NGF were identified through immunohistochemical staining. CONCLUSIONS: The degree of diabetic cystopathy in OLETF rats was changed by duration of type 2 diabetes mellitus. Our results showed that the changes in the bladder in type 2 diabetes mellitus can be identified through a new rat model.