{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T12:18:58Z","timestamp":1754396338813,"version":"3.41.2"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>The urinary bladder is markedly enlarged in the type 1 diabetes mellitus model of streptozotocin-injected rats, which may contribute to the frequent diabetic uropathy. Much less data exists for models of type 2 diabetes. Diabetic polyuria has been proposed as the pathophysiological mechanism behind bladder enlargement. Therefore, we explored such a relationship across nine distinct rodent models of diabetes including seven models of type 2 diabetes\/obesity by collecting data on bladder weight and blood glucose from 16 studies with 2\u20138 arms each; some studies included arms with various diets and\/or pharmacological treatments. Data were analysed for bladder enlargement and for correlations between bladder weight on the one and glucose levels on the other hand. Our data confirm major bladder enlargement in streptozotocin rats and minor if any enlargement in fructose-fed rats, db\/db mice and mice on a high-fat diet; enlargement was present in some of five not reported previously models. Bladder weight was correlated with blood glucose as a proxy for diabetic polyuria within some but not other models, but correlations were moderate to weak except for RIP-LCMV mice (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup> of pooled data from all studies 0.0621). Insulin levels also failed to correlate to a meaningful extent. Various diets and medications (elafibranor, empagliflozin, linagliptin, semaglutide) had heterogeneous effects on bladder weight that often did not match their effects on glucose levels. We conclude that the presence and extent of bladder enlargement vary markedly across diabetes models, particularly type 2 diabetes models; our data do not support the idea that bladder enlargement is primarily driven by glucose levels\/glucosuria.<\/jats:p>","DOI":"10.3389\/fphys.2022.923555","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T04:29:30Z","timestamp":1659932970000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Analysis of 16 studies in nine rodent models does not support the hypothesis that diabetic polyuria is a main reason of urinary bladder enlargement"],"prefix":"10.3389","volume":"13","author":[{"given":"Zeynep E.","family":"Yesilyurt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Matthes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith","family":"Hintermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara R.","family":"Casta\u00f1eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Elvert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus H.","family":"Beltran-Ornelas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana L.","family":"Silva-Velasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimo","family":"Kannt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urs","family":"Christen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Centuri\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huige","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Pautz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebru","family":"Arioglu-Inan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin C.","family":"Michel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2086","DOI":"10.2337\/dbi20-0001","article-title":"Subtypes of type 2 diabetes determined from clinical parameters","volume":"69","author":"Ahlqvist","year":"2020","journal-title":"Diabetes"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/nau.23490","article-title":"A systematic review of urinary bladder hypertrophy in experimental diabetes: part I. Streptozotocin-induced rat models","volume":"37","author":"Arioglu Inan","year":"2018","journal-title":"Neurourol. Urodyn."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1016\/j.juro.2009.02.018","article-title":"Bother related to bladder control and health care seeking behavior in adults in the United States","volume":"181","author":"Benner","year":"2009","journal-title":"J. Urol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1111\/luts.12156","article-title":"Metabolic syndrome induced bladder cannabinoid receptor changes in the fructose-fed rats","volume":"10","author":"Chen","year":"2018","journal-title":"LUTS Low. Urin. Tract. Symptoms"},{"key":"B5","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.semnephrol.2005.09.009","article-title":"Diabetic uropathy","volume":"26","author":"Daneshgari","year":"2006","journal-title":"Semin. Nephrol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/s0022-5347(17)35001-2","article-title":"Comparison of urinary bladder function in rats with hereditary diabetes insipidus, streptozotocin-induced diabetes mellitus, and nondiabetic osmotic diuresis","volume":"151","author":"Eika","year":"1994","journal-title":"J. Urol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1002\/nau.23786","article-title":"A systematic review of urinary bladder hypertrophy in experimental diabetes: part 2. Comparison of animal models and functional consequences","volume":"37","author":"Ellenbroek","year":"2018","journal-title":"Neurourol. Urodyn."},{"key":"B8","doi-asserted-by":"crossref","first-page":"819","DOI":"10.2337\/diab.43.6.819","article-title":"Reversability of diabetes- and diuresis-induced alterations in rat bladder dome muscarinic receptors","volume":"43","author":"Fukumoto","year":"1994","journal-title":"Diabetes"},{"key":"B9","doi-asserted-by":"publisher","first-page":"R23","DOI":"10.1530\/JOE-21-0067","article-title":"100 years of insulin: a brief history of diabetes genetics: insights for pancreatic beta-cell development and function","volume":"250","author":"Ikle","year":"2021","journal-title":"J. Endocrinol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.eururo.2008.01.027","article-title":"Symptom bother and health care-seeking behavior among individuals with overactive bladder","volume":"53","author":"Irwin","year":"2008","journal-title":"Eur. Urol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"149452","DOI":"10.1155\/2013\/149452","article-title":"Animal models of diabetic neuropathy: progress since 1960s","volume":"2013","author":"Islam","year":"2013","journal-title":"J. Diabetes Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.urology.2008.12.077","article-title":"Burden of illness associated with lower urinary tract symptoms including overactive bladder\/urinary incontinence","volume":"74","author":"Kannan","year":"2009","journal-title":"Urology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1111\/j.1476-5381.2010.00872.x","article-title":"Animal research: reporting in vivo experiments: the ARRIVE guidelines","volume":"160","author":"Kilkenny","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"949","DOI":"10.2337\/diab.37.7.949","article-title":"Diabetes and diuretic-induced alterations in function of rat urinary bladder","volume":"37","author":"Kudlacz","year":"1988","journal-title":"Diabetes"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e2915","DOI":"10.1002\/dmrr.2915","article-title":"Animal models of human type 1 diabetes for evaluating combination therapies and successful translation to the patient with type 1 diabetes","volume":"33","author":"Lenzen","year":"2017","journal-title":"Diabetes. Metab. Res. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"F1220","DOI":"10.1152\/ajprenal.00449.2004","article-title":"Alterations in neurogenically mediated contractile responses of urinary bladder in rats with diabetes","volume":"288","author":"Liu","year":"2005","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1161\/CIRCRESAHA.116.309115","article-title":"Decline in cardiovascular mortality: possible causes and implications","volume":"120","author":"Mensah","year":"2017","journal-title":"Circ. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"R833","DOI":"10.1152\/ajpregu.00093.2021","article-title":"Function and morphology of the urinary bladder after denervation","volume":"320","author":"Michel","year":"2021","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1007\/s00210-015-1134-1","article-title":"A comprehensive review of the pharmacodynamics of the SGLT2 inhibitor empagliflozin in animals and humans","volume":"388","author":"Michel","year":"2015","journal-title":"Naunyn. Schmiedeb. Arch. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1124\/mol.119.118927","article-title":"New author guidelines for displaying data and reporting data analysis and statistical methods in experimental biology","volume":"97","author":"Michel","year":"2020","journal-title":"Mol. Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/S0302-2838(02)00041-6","article-title":"Symptomatic benign prostatic hyperplasia: impact on partners' quality of life","volume":"41","author":"Mitroupoulos","year":"2002","journal-title":"Eur. Urol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1111\/bph.15193","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"177","author":"Percie du Sert","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1111\/j.1476-5381.1994.tb16193.x","article-title":"Factors underlying the increased sensitivity to field stimulation of urinary bladder strips from streptozotocin-induced diabetic rats","volume":"113","author":"Tammela","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1016\/s0022-5347(01)67393-2","article-title":"Temporal changes in micturition and bladder contractility after sucrose diuresis and streptozotocin-induced diabetes mellitus in rats","volume":"153","author":"Tammela","year":"1995","journal-title":"J. Urology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e100046","DOI":"10.1136\/bmjos-2019-100046","article-title":"Systematic review of guidelines for internal validity in the design, conduct and analysis of preclinical biomedical experiments involving laboratory animals","volume":"4","author":"Vollert","year":"2020","journal-title":"BMJ Open Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.juro.2012.08.222","article-title":"Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes","volume":"189","author":"Xiao","year":"2013","journal-title":"J. Urol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"911","DOI":"10.3389\/fphar.2019.00911","article-title":"Urinary bladder weight and function in a rat model of mild hyperglycemia and its treatment with dapagliflozin","volume":"10","author":"Yesilyurt","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"S141","DOI":"10.1002\/nau.24746","article-title":"Effects of the sodium-glucose transporter 2 inhibitor empagliflozin on bladder size, contraction and relaxation in a rat model of type 1 diabetes","volume":"42","author":"Yesilyurt","year":"2021","journal-title":"Neurourol. Urodyn."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.923555\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T04:29:36Z","timestamp":1659932976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.923555\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,8]]},"references-count":28,"alternative-id":["10.3389\/fphys.2022.923555"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.923555","relation":{},"ISSN":["1664-042X"],"issn-type":[{"type":"electronic","value":"1664-042X"}],"subject":[],"published":{"date-parts":[[2022,8,8]]},"article-number":"923555"}}