Review of Erectile Dysfunction in Diabetic Animal Models

Abstract

Erectile dysfunction (ED) is a common, male sexual disorder that has a negative impact on the quality of life of men and their sexual partners. The prevalence of ED in diabetic men is ≥ 50%. Animal models provide a valuable perspective in the investigation of ED. Most basic science studies have utilized the rodent model of type 1 diabetes. However, an animal model for type 2 diabetes-associated ED requires verification. The streptozotocin (STZ) induced type 1 diabetic model has contributed to significant advancement in the study of ED. A Medline search using the keywords "diabetic animals and ED" was performed, and available peer-reviewed English articles between 2007-2013 were evaluated. The proposed mechanisms for developing ED in diabetics include: hyperglycemia, impaired nitric oxide (NO) synthesis, cyclic guanosine monophosphate (cGMP) pathway dysfunction, increased levels of reactive free-radicals, up-regulation of the RhoA/Rho-kinase pathway, and neuropathic damage. The current treatment regimen of diabetes-induced ED is multimodal. Modification of comorbidities and, specifically, rectifying the underlying hyperglycemia is vital to prevent or halt progression of the disease. Further research on the basic mechanisms of ED and additional studies using better animal models of ED associated with type 1 and 2 diabetes are needed. Preclinical studies using the diabetic animal model will likely provide further insight for intervention and prevention strategies for diabetic ED treatment.

Low molecular weight fucoidan ameliorates streptozotocin-induced hyper-responsiveness of aortic smooth muscles in type 1 diabetes rats

“…In addition, upregulated oxidative stress and disturbed prostanoids generation occurred in the endothelium-denuded aortas of the STZ rats, again, demonstrating typical impairment of vessels in type 1 diabetes (Gur et al, 2014;Shi and Vanhoutte, 2008;Van Dyke et al, 2008). Importantly, the current study suggested that intervention of the STZ rats with LMWF profoundly ameliorated these diabetes-associated disorders, based on the observations that 1) LMWF reduced the over-contraction of aortic smooth muscles in response to phenylephrine in the diabetic rats, hence improved blood pressure; 2) LMWF ameliorated STZ-elicited hyperlipidaemia by decreasing the level of TC, LDL-C and TG;…”

“…During diabetes, oxidative stress and/or COX takes part not only in the dysfunction of the endothelium but also in that of vascular smooth muscles, therefore the present experiments were designed to study the contribution of oxidative stress and COX to the abnormal responsiveness of aortic smooth muscles, observed in streptozotocin (STZ)-induced rats for they manifest stable pathological features that resemble human type 1 diabetes with hyperglycemia, hypertension, and development of vascular complications (Gur et al, 2014;Van Dyke et al, 2010). This study evaluated the in vivo effects of LMWF on blood pressure and lipid profiles, and its ex vivo effects on endothelium-independent vessel contraction, and measured the levels of ROS and COXderived prostanoids in the endothelium-denuded aortas, and simultaneously compared them with the effects of probucol, a lipid-modifying drug with powerful antioxidant and anti-inflammatory properties (Cui et al, 2014).…”

A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats

“…The STZ induced type 1 diabetic model has contributed to significant advancement in the study of ED (Gur et al 2014). It is a well-accepted erectile dysfunction animal model (Li et al 2012;Liu et al 2015;Wang et al 2015).…”

“…The possible mechanisms for diabetic ED include hyperglycemia, impaired nitric oxide (NO) synthesis, cyclic guanosine monophosphate (cGMP) pathway dysfunction, increased levels of reactive free-radicals, up-regulation of the RhoA/Rho-kinase pathway, and neuropathic damage (Gur et al 2014). The hyperglycemic conditions in diabetes may cause oxidative stress, which impairs the function of endothelium and nerve in the penile tissue and decreases the synthesis of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) (Bivalacqua et al 2003;Li et al 2012).…”

137 Superparamagnetic Iron Oxide Nanoparticle Targeting of Adipose Tissue-Derived Stem Cells in Diabetes-Associated Erectile Dysfunction

“…2 A more in-depth discussion of the pathophysiology is available in reviews elsewhere. 3,4 The efficacy of oral medications such as tadalafil, vardenafil, and sildenafil, which are generally considered as first-line treatments for ED, is lower in these patients compared with nondiabetic patients. 5 Recent studies have focused on cellular therapy of DED, and each cell type has been shown to be effective in an animal study.…”