Abstract
Hypertrophy and dysfunction of the urinary bladder are consistently observed in animal models of type 1 and less consistently in those of type 2 diabetes. We have tested the effects of mild hyperglycemia (n = 10 per group) in a randomized, blinded study and, in a blinded pilot study, of type 2 diabetes (n = 6 per group) and its treatment with dapagliflozin (1 mg/kg per day) on weight, contraction, and relaxation of the rat bladder. Based on a combination of high-fat diet and a low dose of streptozotocin, animals in the main study reached a mean peak blood glucose level of about 300 mg/dl, which declined to 205 mg/dl at study end. This was associated with a small, if any, increase in bladder weight. In a pooled analysis of all animals of the main and the pilot study, we detected a correlation of moderate strength between blood glucose and bladder weight (r 2 = 0.2013; P = 0.0003 for Pearson correlation coefficient). Neither the main nor the pilot study found evidence for an altered contractility (responses to carbachol or KCl) or relaxation (responses to isoprenaline, fenoterol, CL 316,243, or forskolin). Treatment with dapagliflozin in the absence of hyperglycemia increased diuresis in the main study by 43% relative to control and increased bladder weight by 15% in the pooled groups of both studies (post hoc analysis). We conclude that mild hyperglycemia has no major effects on bladder hypertrophy or function.
Highlights
More than 400 million people globally suffer from diabetes mellitus, and numbers are rising (World Health Organization, 2016)
Treatment with dapagliflozin had no major effect on glucose levels in control animals, it further reduced them to about 130 mg/dl in high-fat diet (HFD)/STZ/dapa rats (Figure 1; Table 1)
Mild hyperglycemia was not associated with enlargement or dysfunction of the urinary bladder in our rat model
Summary
More than 400 million people globally suffer from diabetes mellitus, and numbers are rising (World Health Organization, 2016). Most of them suffer from type 2 diabetes mellitus (T2DM). In general, and bladder dysfunction in particular are estimated to occur in 80% and 50% of all diabetic patients, respectively (Daneshgari and Moore, 2006). Injection of streptozotocin (STZ) is the most frequently used animal model of type 1 diabetes mellitus (T1DM), and STZ-injected rats consistently exhibit bladder hypertrophy, by average, a doubling of bladder weight (Arioglu Inan et al, 2018). Despite the much greater incidence of T2DM as compared with T1DM, only a few studies have assessed bladder weight in models of T2DM. These models have yielded heterogeneous results with some models, such as Bladder Hypertrophy in Hyperglycemic Rats
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