Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat

Abstract

Despite the fact that urogenito-sexual complications significantly impact the quality of life of diabetic patients, a robust in vivo experimental model is lacking. Bladder and erectile function in the Type 2 diabetic Goto-Kakizaki (GK) rat and responses to standard-of-care treatments for each disorder have been assessed. GK rats (n = 25, 18-wk-old, GK/Par colony) and age-matched Wistar rats (n = 23), characterized for their metabolic parameters, were used. Bladder function was assessed by cystometry in conscious rats treated by intravenous solifenacin (1 mg/kg). Subsequently, erectile function was assessed under anesthesia following electrical stimulation of the cavernous nerve in presence of intravenous sildenafil (0.3 mg/kg). GK rats displayed detrusor overactivity with a significant increase in frequency/amplitude of nonvoiding contractions during the filling phase, together with an increase in bladder capacity, intercontraction interval, voided volume, and maximal pressure of voiding contraction. Solifenacin significantly decreased parameters characterizing voiding contractions without modifying voiding efficiency. Erectile function in GK rats was markedly impaired and remained so after sildenafil treatment despite a significant improvement. GK rats display both bladder and erectile dysfunctions and respond at least partially to standard-of-care treatments for each disorder, thus representing a suitable model to investigate the pathophysiology and assess the efficacy of new therapeutic agents for Type 2 diabetes-associated bladder and erectile complications.

Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes

“…glucose clamping, b-cell function in patients remained significantly impaired in comparison with non-obese control subjects (Dutia et al 2014). In our in situ pancreatic perfusion experiment, first-phase insulin secretion was improved in the GK groups, which is encouraging because the major defect of b-cell function in GK rats is first-phase insulin secretion (Oger-Roussel et al 2013). However, both basal and first-phase insulin secretion were still significantly lower than levels in Wistar.…”

A systematic review of urinary bladder hypertrophy in experimental diabetes: Part 2. Comparison of animal models and functional consequences

“…Other investigators also did not observe changes in cystometric parameters in 10‐week‐old Goto‐Kakizaki rats, whereas they noted increased BC, voided volume and bladder compliance accompanied by reduced micturition threshold and peak pressure at 46‐week‐old animals; of note, the changes in the latter group occurred in the absence of bladder hypertrophy. A third study in 18‐week‐old Goto‐Kakizaki rats reported increased BC and micturition volume, unchanged basal or threshold pressure and voiding efficiency and lowered micturition frequency; frequency and amplitude of non‐voiding contractions was increased . Acute administration of the muscarinic receptor antagonist solifenacin similarly reduced micturition pressure in both strains whereas it reduced duration of micturition only in control and not in diabetic animals.…”

“…Hereditary models of T2DM include the Goto‐Kakizaki rat, a model with moderately increased blood glucose levels (Supplementary Table S1). Three studies have reported on bladder hypertrophy in Goto‐Kakizaki rats as compared to an euglycemic control strain, having looked at 12 and 70 weeks, 10 and 46 weeks, or 18 weeks old animals . They report a BW of 88‐132% of control and a BBW of 104‐131% of control (Figure , Supplementary Table S1), that is, only moderate if any enlargement.…”

Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction

“…Basic scientific studies indicate that increased oxidative stress and reduced nitric oxide (NO) bioavailability are the major derangements underlying the development and progression of vasculogenic and neurogenic ED associated with DM (Long et al, 2012; Vernet et al, 1995; Luttrell et al, 2008; Carneiro et al, 2010; Elliati et al, 2013; Albersen et al, 2011; Chiou et al, 2010; Oger et al, 2014; Kataoka et al 2014; Musicki et al, 2016; Xie et al, 2007; Kovanecz et al, 2009; Chitaley 2009; Nunes et al, 2015; Wingard et al, 2007; Sanchez et al, 2012). In diabetic patients ED is similarly related to reduced NOS activity, as evidenced by elevated arginase activity (Bivalacqua et al, 2001) and decreased nNOS protein expression (Dashwood et al, 2011), nitrate/nitrite (Tuncayengin et al, 2003) and cGMP content (Angulo et al, 2010).…”