High glucose exposure leads to increased cellular senescence of bladder smooth muscle cells; a role of bladder smooth muscle dysfunction in diabetic bladder dysfunction

Abstract

Diabetic bladder dysfunction affects 30-50% of all diabetes patients and is characterized by symptoms of overactive and underactive bladder, which greatly impacts quality of life. Diabetes is correlated with increased cellular senescence. Senescence is a physiologic phenomenon; however, chronic high levels can lead to tissue dysfunction. Multiple in vitro studies have shown that high glucose exposure results in an increase in cellular senescent cells. The smooth muscle layer of the bladder is responsible for contraction and relaxation of the bladder; therefore, we hypothesize that primary bladder smooth muscle cells exposed to a high glucose environment will result in an increased number of cellular senescent cells. Rat primary bladder smooth muscle cells were incubated in normal glucose (5.5mM), high glucose (22mM), high mannitol (22mM), and bleomycin (50𝜇g/ml). A beta-galactosidase assay was utilized to visualize the presence of senescent cells. Cells treated with high glucose exhibited increased cellular senescent cells compared to both normal and high mannitol control. We conclude that high glucose exposure increases cellular senescence in primary bladder smooth muscle cells. An increased amount of cellular senescence within the smooth muscle layer of the bladder could contribute to bladder dysfunction as seen with diabetes.