Effects of Vibegron, a β₃-Adrenoceptor Agonist, on Lower Urinary Tract Dysfunction in Diabetic Rats

In this study, we aimed to investigate the impact of vibegron, a β₃-adrenergic receptor agonist, on lower urinary tract dysfunction in a diabetic rat model.

Female rats were categorized into three groups: non-diabetic controls (N), streptozotocin-induced diabetic rats receiving vehicle (D), and diabetic rats treated with vibegron (DV). In the DV group, vibegron was administered orally at 30 mg/kg/day starting 7-8 weeks after diabetes induction. At 8 weeks post-induction, voiding assays, urinary 8-hydroxydeoxyguanosine (8-OHdG) measurements, cystometry, and analysis of bladder mRNA expression levels of ischemia- and inflammatory-related markers were performed.

The 24-h voiding assays showed that Groups D and DV had markedly higher urine volume, average voided volume, voiding frequency, and water intake compared to Group N. Urinary 8-OHdG levels were markedly elevated in Group D than those in Groups N and DV. Group D also exhibited higher opening pressure and non-voiding contractions. Intercontraction intervals, voided volume, post-void residual volume, bladder capacity, and compliance were significantly increased, while voiding efficiency was markedly decreased in Groups D and DV compared to that in Group N. Bladder mRNA expression of hypoxia-inducible factor-1 alpha (Hif1a), vascular endothelial growth factor A (Vegfa), transforming growth factor-beta 1 (Tgfb1), and tumor necrosis factor alpha (Tnfa) was upregulated in Group D compared with that in Groups N and DV.

These findings suggest that vibegron may be a promising therapeutic option for addressing detrusor overactivity, ischemia, and inflammation of the bladder associated with diabetes mellitus.