Bladder Enlargement Correlates with Plasma Insulin, Not Glucose Levels in Fructose‐Fed Rats

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IntroductionMajor bladder enlargement is observed in many, but not all rodent models of diabetes (Neurourol Urodyn 37: 2346–2360, 2018). According to one theory, bladder enlargement occurs secondary to increased diuresis, which in turn occurs secondary to high plasma glucose levels. However, comparisons across models show only moderate correlations between bladder enlargement and glucose levels. In a recent analysis, we found that correlations within models are tight in some (e.g. rat insulin promotor lymphocytic choriomeningitis virus mice), but weak to non‐existent in other models (e.g. insulin receptor substrate 2 knock‐out or ob/ob mice). Therefore, we have expanded our investigation to another model, fructose‐fed rats.Methods7‐week old male Wistar rats received tap water or water containing 15% fructose for 20 weeks (n = 6 per group). At the end of treatment, an oral glucose tolerance test with quantification of plasma glucose and insulin levels at various time points was performed; bladder and body weight were determined.ResultsWhile basal glucose and glucose area under the curve (AUC) during the glucose tolerance test were similar in both groups, basal insulin and AUC were increased in fructose fed rats (basal mean difference 0.46 mIU/ml*120 min (95% CI 0.17; 0.75)), indicating insulin resistance. Bladder weight was greater in fructose‐fed rats (mean difference 79 mg (95% CI 56; 102)). Bladder weight did not correlate with basal glucose or AUC, but with basal insulin and, somewhat weaker, AUC (r2 0.5127 and 0.3321).ConclusionsWe propose that insulin rather than glucose levels may be the driver of bladder enlargements in some models of diabetes and hyperinsulinemia.Support or Funding InformationDeutsche Forschungsgemeinschaft Mi 294/8‐1; Conacyt Mexico 252702; Ankara University BAP‐16L0237006; Scientific and Technological Research Council of Turkey TUBITAK SBAG‐115S564 and TUBİTAK‐2211/ACorrelation of bladder weight with glucose and insulin levelsFigure 1