Analysis of 16 studies in nine rodent models does not support the hypothesis that diabetic polyuria is a main reason of urinary bladder enlargement.

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 2-8 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 (r 2 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.

Normalization of organ bath contraction data for tissue specimen size: does one approach fit all?

Organ bath experiments are a key technology to assess contractility of smooth muscle. Despite efforts to standardize tissue specimen sizes, they vary to a certain degree. As it appears obvious that a larger piece of tissue should develop greater force, most investigators normalize contraction data for specimen size. However, they lack agreement which parameter should be used as denominator for normalization. A pre-planned analysis of data from a recent study was used to compare denominators used for normalization, i.e., weight, length, and cross-sectional area. To increase robustness, we compared force with denominator in correlation analysis and also coefficient of variation with different denominators. This was done concomitantly with urinary bladder strips and aortic rings and with multiple contractile stimuli. Our urinary bladder data show that normalization for strip weight yielded the tightest but still only moderate correlation (e.g., r2 = 0.3582 for peak carbachol responses based on 188 strips). In aorta, correlations were even weaker (e.g., r2 = 0.0511 for plateau phenylephrine responses normalized for weight based on 200 rings). Normalization for strip size is less effective in reducing data variability than previously assumed; the normalization denominator of choice must be identified separately for each preparation.