To better understand the relevance of bladder hypertrophy in many models of experimental diabetes, more studies in models of type 2 diabetes are urgently needed. Moreover, the role of factors other than hypertrophy in the genesis of bladder dysfunction requires further exploration.

Aims:To better understand the genesis and consequences of urinary bladder hypertrophy in animal models of diabetes. This part of a three-article series will analyze urinary bladder hypertrophy in the diabetes mellitus type 1 model of rats injected with streptozotocin (STZ). Methods: A systematic search for the key word combination "diabetes," "bladder"and "hypertrophy" was performed in PubMed; additional references were identified from reference lists of those publications. All papers were systematically extracted for relevant information. Results: A total of 39 studies were identified that quantitatively reported on bladder hypertrophy in rats upon injection of STZ; of which several reported on multiple time points yielding a total of 83 group comparisons. Bladder hypertrophy was found consistently, being fully developed as early as 1 week after STZ injection (bladder weight 188 ± 59% of matched control). Hypertrophy was similar across sexes and STZ doses (35-40 vs 50-65 mg/kg) but appeared greater with Wistar rats than other rat strains. The extent of bladder hypertrophy was not correlated to blood glucose concentrations, but normalization of blood glucose concentration by insulin treatment starting early after STZ injection prevented hypertrophy; insulin treatment starting after hypertrophy had established largely reversed it. Conclusions: Bladder size approximately doubles after STZ injection in rats; the extent of hypertrophy is not linked to the severity of hyperglycemia but largely reversible by restoration of euglycemia. K E Y W O R D Sbladder, diabetes, hypertrophy, insulin, rat strain, streptozotocinThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Mechanical activity of the heart is adversely affected with metabolic syndrome (MetS) characterized with increased body-mass and marked insulin-resistance.Herein, we examined effects of high-carbohydrate intake on cardiac functional abnormalities via evaluating in situ heart-work, heart-rate and electrocardiograms (ECG) in rats. MetS is induced in Wistar male rats by adding 32% sucrose for 22-24 weeks and confirmed with insulin-resistance, increased body-weight, blood glucose and insulin, systolic and diastolic blood pressures besides significant left ventricular integrity-lost and increased connective-tissue around myofibrils. Analysis of in situ ECG-recordings showed markedly shorten QT-interval and depressed QRP with increased heart-rate. We also observed augmented oxidative stress and decreased antioxidant defense characterized with decreases in serum total thiol-level and attenuated paraoxonase and arylesterase activities. Our data clearly indicate that increased heart-rate and shortened QT-interval concomitant with higher left ventricular developed pressure responses to β-adrenoreceptor stimulation as a result of less cAMP-release could be regarded as natural compensation mechanisms in overweight MetS rats. Since MetS leads further to persistent insulin-resistance and obesity, one should get into consideration these important facts associated with onset of the depressed heart-work, the increased heart-rate and shorten QT-interval in highcarbohydrate intake, which will possible lead to more deleterious effects on mammalian heart.

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β-Adrenoceptors (AR) stimulate cardiac Na/K pump in healthy hearts. β-ARs are upregulated by persistent sympathetic hyperactivity; however, their effect on Na/K ATPase activity and ventricular function in this condition is still unknown. Here, we investigate preventive effects of additional β-AR activation (BRL) on Na/K ATPase activity and in vivo hemodynamics in a model of noradrenaline-induced hypertrophy. Rats received NA or NA plus simultaneously administered BRL in vivo infusion for 14 days; their cardiac function was investigated by left ventricular pressure-volume analysis. Moreover, fibrosis and apoptosis were also assessed histologically. NA induced an hypertrophic pattern, as detected by morphological, histological, and biochemical markers. Additional BRL exposure reversed the hypertrophic pattern and restored Na/K ATPase activity. NA treatment increased systolic function and depressed diastolic function (slowed relaxation). Additional BRL treatment reversed most NA-induced hemodynamic changes. NA decreased Na/K pump α2 subunit expression selectively, a change also reversed by additional BRL treatment. Increasing β-AR stimulation may prevent the consequences of chronic NA exposure on Na/K pump and in vivo hemodynamics. β-AR agonism may thus represent a new therapeutic strategy for pharmacological modulation of hypertrophy under conditions of chronically enhanced sympathetic activity.