AB108. The changes of detrusor relaxation capacity and βreceptor expressions in type 2 diabetic rats

OBJECTIVE: To investigate the changes in relaxation capacity and expression of β receptors with the progression of type 2 diabetes mellitus in SD rat model. METHODS: Detrusor strips, when stimulated in vitro by isoprenaline, a β receptor, at increasing concentrations (1×10(-9)–3×10(-5)), were employed to conduct the contraction/relaxation test. This may allow the determination of the changes in contractility at various time points in rats with diabetes mellitus (DM) and normal controls. Flow cytometry was adopted to examine the alteration in β3 receptors on the cellular membrane following digestion of detrusor cells. The cells of bladder were homogenized for subsequent assessment of the changes in G protein subtypes at various time points by Western blotting. RESULTS: In our present study, detrusor strips were subjected to isoprenaline stimulation at various concentrations, rats with DM were associated with a lower half maximal inhibitory concentration (IC50) yet higher maximal distention (Emax) when compared with normal controls at week 8 (P<0.05 and 0.01, respectively). An opposite trend was noted at week 16 (P<0.01 and 0.05, respectively). A lower IC50 and profoundly reduced Emax were found in rats with DM at week 24 (both P<0.01). At week 8, rats with DM yielded increased expression of β3 receptors on the cellular membrane (P<0.05). However, suppression of β3 receptor expression was noted at week 16 when compared with that of normal controls (P<0.05), as suggested by the intensity of fluorescence. The reduction in β3 receptor expression in rats with DM was further aggravated at week 24 (P<0.01). CONCLUSIONS: Increased relaxation capacity is associated with a higher sensitivity to isoprenaline at the early stage of disease in rats with DM, the results that coincided with raised, but not suppressed, β3 receptor expression in the detrusor that could have stemmed from compensation.