• Wei-Chia Lee, Kay L H Wu, You-Lin Tain, Steve Leu, Yuan-Tso Cheng, and ChanJulie Y HJYHInstitute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. Electronic address: jchan@cgmh.org.tw..
• Division of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
• J Formos Med Assoc. 2023 Mar 1; 122 (3): 258266258-266.

Background/PurposeMetabolic syndrome (MetS) and overactive bladder might share common pathophysiologies. Environmental fructose exposure during pre- and postnatal periods of rats may program MetS-associated bladder overactivity. We explored the dysregulated insulin signalling at bladder mucosa, as a common mechanism, in facilitating bladder overactivity in rats with MetS induced by maternal and post-weaning fructose diet.MethodsMale offspring of Sprague-Dawley rats were subject into 4 groups by maternal and post-weaning diets (i.e., Control/Control, Fructose/Control, Control/Fructose and Fructose/Fructose by diets). Micturition behavior was evaluated. Acidic ATP solution was used to elicit cystometric reflex along with insulin counteraction. Concentration-response curves to insulin were plotted. The canonical signalling pathway of insulin was evaluated in the bladder mucosal using Western blotting. Levels of detrusor cGMP and urinary NO2 plus NO3 were measured.ResultsMale offspring with any fructose exposure presents traits of MetS and bladder overactivity. We observed all fructose exposure groups have the poor urodynamic response to insulin during ATP solution stimulation and poor insulin-activated detrusor relaxation in organ bath study. Compared to controls, the Control/Fructose and Fructose/Fructose groups showed the increased phosphorylation levels of IRS1 (Ser307) and IRS2 (Ser731); thus, suppressed the downstream effectors and urinary NOx/detrusor cGMP levels. The Fructose/Control group showed the compensatory increase of phospho-AKT (Ser473) and phospho-eNOS/eNOS levels, but decreased in eNOS, phospho-eNOS, urinary NOx, and detrusor cGMP levels.ConclusionOur results show dysregulated insulin signalling at bladder mucosa should be a common mechanism of MetS-associated bladder overactivity programmed by pre-and postnatal fructose diet.Copyright © 2022. Published by Elsevier B.V.

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