Erdogan Betül R, Michel Martina B, Matthes Jan, Castañeda Tamara R, Christen Urs, Arioglu-Inan Ebru, Michel Martin C, Pautz Andrea
Department of Pharmacology, Faculty of Pharmacy, Izmir Katip Celebi University, Izmir, Türkiye.
Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany.
Front Pharmacol. 2023 Feb 20;14:1118730. doi: 10.3389/fphar.2023.1118730. eCollection 2023.
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. 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). 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. We conclude that sex differences in diabetes/obesity-associated bladder enlargement may be model dependent.
糖尿病常导致下尿路功能障碍。在糖尿病动物模型中，膀胱功能障碍最常评估的参数是膀胱增大，这在1型糖尿病中始终可见，而在2型糖尿病中则不太一致。绝大多数关于糖尿病和肥胖动物模型膀胱重量的研究是在雄性动物中进行的，尚无研究直接比较两性之间的这一结果参数。因此，我们比较了五种肥胖和糖尿病小鼠模型（RIP-LCMV、db/db、ob/ob（两项研究）、胰岛素受体底物2（IRS2）基因敲除小鼠和高脂饮食小鼠；对先前报道研究的预先指定的二次分析）的膀胱重量和膀胱/体重比。在所有研究对照组的汇总分析中，雌性小鼠的血糖水平略低、体重较轻且膀胱重量较低，但两性的膀胱/体重比相似（0.957对0.986mg/g，平均差异0.029[-0.06；0.118]）。在六个糖尿病/肥胖组中，有三组两性的膀胱/体重比相似，而在其他三组中雌性小鼠的该比值较小。一组与膀胱增大和/或纤维化及炎症病理生理学相关的基因的mRNA表达在两性之间没有系统性差异。我们得出结论，糖尿病/肥胖相关膀胱增大的性别差异可能取决于模型。
