gms | German Medical Science

Introduction: Tissue hypertrophy is typically accompanied by fibrosis. A notable exception is the urinary bladder in streptozotocin-induced type 1 diabetes (T1DM) in rodents. Whether bladder fibrosis develops in animal models of type 2 diabetes (T2DM) is unknown.

Methods: Five rodent models were studied: STZ-induced T1DM in rats as positive control; ZSF rats, rats exposed to high-fat diet (HFD) + low-dose STZ, and ob/ob and db/db mice as T2DM models. The presence of fibrosis was assessed by Masson-Goldner staining; additionally, mRNA expression of collagen I and III and of TGF-β was assessed by qPCR with double normalization for β-actin and GAPDH.

Results: STZ, HFD+STZ and ZSF rats exhibited marked bladder enlargement (about doubled weight) and ob/ob mice a moderate bladder enlargement, whereas db/db mice did not (negative control). None of the five models exhibited a major increase in connective tissue staining, for instance STZ rats +16% [95% CI -9;+41], ZSF rats -29% [95% CI -11;-47], and ob/ob mice 0% [-12;+12]. The mRNA expression of collagens I and III and of TGF-β was not increased in any of the models, for instance collagen I in STZ rats -19% [-87;+48], in ZSF rats +20% [-45;+84], and ob/ob mice -42% [-60;-24].

Conclusion: We conclude that lack of fibrosis despite major enlargement of the urinary bladder is not limited to rodent models of T1DM but also seen in those of T2DM. These data further support that the pathophysiology of diabetes-associated bladder enlargement differs from that of non-diabetic causes of bladder hypertrophy.

Conflict of interest: TC and AK are former employees of Sanofi-Aventis. MCM is a consultant to Boehringer Ingelheim. The other authors report no conflict of interest.

This work was funded by DFG Mi 294-10/1 and TÜBITAK-SBAG 118S443. ÖB and AA were supported by fellowships from Erasmus+ and Deutscher Akademischer Auslandsdienst, respectively.