A comparison of urinary bladder weight in male and female mice across five models of diabetes and obesity

Betül R Erdogan; Martina B Michel; Jan Matthes; Tamara R Castañeda; Urs Christen; Ebru Arioglu-Inan; Martin C Michel; Andrea Pautz

doi:10.3389/fphar.2023.1118730

A comparison of urinary bladder weight in male and female mice across five models of diabetes and obesity

Front Pharmacol. 2023 Feb 20:14:1118730. doi: 10.3389/fphar.2023.1118730. eCollection 2023.

Authors

Betül R Erdogan¹, Martina B Michel², Jan Matthes³, Tamara R Castañeda⁴, Urs Christen⁵, Ebru Arioglu-Inan⁶, Martin C Michel², Andrea Pautz²

Affiliations

¹ Department of Pharmacology, Faculty of Pharmacy, Izmir Katip Celebi University, Izmir, Türkiye.
² Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany.
³ Centre of Pharmacology, University Medical Center, University of Cologne, Cologne, Germany.
⁴ Sanofi Research and Development, Frankfurt, Germany.
⁵ Pharmazentrum, Goethe University, Frankfurt, Germany.
⁶ Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Türkiye.

Abstract

Introduction: Diabetes often leads to lower urinary tract dysfunction. The most frequently assessed parameter of urinary bladder dysfunction in animal models of diabetes is an enlargement of the bladder, which is consistently observed in type 1 and less consistently in type 2 diabetes. The vast majority of studies on bladder weight in animal models of diabetes and obesity has been performed in males, and no studies have directly compared this outcome parameter between sexes. Methods: Therefore, we have compared bladder weight and bladder/body weight ratio in five mouse models of obesity and diabetes (RIP-LCMV, db/db, ob/ob (two studies), insulin receptor substrate 2 (IRS2) knock-out mice and mice on a high-fat diet; pre-specified secondary analysis of a previously reported study). Results: In a pooled analysis of the control groups of all studies, females exhibited slightly lower glucose levels, lower body weight, and lower bladder weight, but bladder/body weight ratio was similar in both sexes (0.957 vs. 0.986 mg/g, mean difference 0.029 [-0.06; 0.118]). Among the six diabetic/obese groups, bladder/body weight ratio was similar in both sexes in three but smaller in female mice in three other groups. The mRNA expression of a panel of genes implied in the pathophysiology of bladder enlargement and/or fibrosis and inflammation did not differ systematically between sexes. Conclusions: We conclude that sex differences in diabetes/obesity-associated bladder enlargement may be model dependent.

Keywords: bladder; diabetes; hypertrophy; mouse; obesity; sex difference.

Grants and funding

This analysis and/or the underlying studies had been funded by Landesoffensive zur Entwicklung wissenschaftlich-ökonomischer Exzellenz (LOEWE; LOEWE Center for Translational Medicine and Pharmacology) of the State of Hessen, Germany (to UC), by TÜBITAK-SBAG 118S443 (to EAI), and by Deutsche Forschungsgemeinschaft Mi 294/10-1 (to MCM). Some underlying studies were performed and funded by Sanofi-Aventis for purposes unrelated to this manuscript. The commercial and non-commercial funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.