{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:23:14Z","timestamp":1786116194278,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK 119482"],"award-info":[{"award-number":["DK 119482"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore molecular mechanisms underlying excessive extracellular adenosine (ADO) accumulation in the bladder lamina propria (LP) of mice with type 2 diabetes (T2D) induced by a high\u2010fat, high\u2010sucrose diet (HFHSD), conceivably leading to bladder underactivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Performing automated, non\u2010invasive, continuous monitoring in metabolic cages, we evaluated 24\u2010h water intake and urine output of male C57Bl\/6 nondiabetic (ND) and HFHSD\u2010T2D mice. Using a detrusor\u2010free bladder model and HPLC with fluorescence detection, we assessed availability of ATP, ADP, AMP, and ADO as well as the degradation of 1\n                      <jats:italic>N<\/jats:italic>\n                      <jats:sup>6<\/jats:sup>\n                      \u2010etheno\u2010ATP (eATP, 2\u2009\u00b5M) in extraluminal solutions (ELS) interfacing with the LP of both nondistended and distended bladders from ND and HFHSD\u2010T2D mice. We also investigated the effect of ENT1 inhibition on transurothelial eADO transport and quantified AMPK\u03b1 expression, its phosphorylation status, and ENT1 protein levels in ND and T2D bladder mucosa using the Jess Protein Western nano\u2010immunoassay. Glass's \u2206 and Hedges' g effect size indicators were used to compare non\u2010diabetic and HFHSD\u2010T2D groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the HFHSD\u2010T2D mice, the number of voids per 24\u2009h was significantly decreased (Glass's \u2206 3.694) whereas urine volume per void was significantly increased (Glass's \u2206 1.554) in comparison with ND mice. Purines were released in ELS\/LP of ND and diabetic bladders. T2D bladders exhibited a marked reduction in ATP (Glass's \u2206 12.772) and a substantial elevation in ADO levels within the ELS of distended preparations (Glass's \u2206 4.472). Hydrolysis of eATP to eADP, eAMP, and eADO was accelerated in the T2D ELS\/LP. AMPK\u03b12 expression and T172 phosphorylation were notably diminished in T2D bladder mucosa (Glass's \u2206\u2009=\u20092.453 and 2.572, respectively). Pharmacological inhibition of ENT1 reduced the transport of eADO from the lumen to the ELS. ENT1 protein levels were significantly lower in T2D bladder mucosa (Glass's \u2206 = 12.824).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Excessive accumulation of the inhibitory purine ADO in the LP of T2D bladders is driven by two convergent mechanisms: (1) accelerated degradation of ATP possibly linked to AMPK dysregulation, and (2) impaired cellular uptake of ADO due to diminished ENT1 expression. Together, these disruptions contribute to elevated extracellular ADO levels, which likely inhibit detrusor muscle contractility and promote the development of an underactive bladder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/nau.70387","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T07:56:01Z","timestamp":1786002961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diabetes\u2010Induced Dysregulation of Purinergic Signaling in the Bladder Mucosa: Accelerated ATP Hydrolysis and Impaired Adenosine Uptake Promote Underactive Bladder Phenotype"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8491-4736","authenticated-orcid":false,"given":"Mahsa","family":"Borhani Peikani","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology University of Nevada Reno School of Medicine Reno Nevada 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