Vasculogenesis and Diabetic Erectile Dysfunction: How Relevant Is Glycemic Control?

Abstract

Erectile dysfunction (ED) is a complication of diabetes, condition responsible for causing endothelial dysfunction (EDys) and hampering repair mechanisms. However, scarce information is available linking vasculogenesis mediated by Endothelial Progenitor Cells (EPCs) and diabetes-associated ED. Furthermore, it remains to be elucidated if glycemic control plays a role on EPCs functions, EPCs modulators, and penile vascular health. We evaluated the effects of diabetes and insulin therapy on bone marrow (BM) and circulating EPCs, testosterone, and systemic/penile Stromal Derived Factor-1 alpha (SDF-1α) expression. Male Wistar rats were divided into groups: age-matched controls, 8-weeks streptozotocin-induced type 1 diabetics, and insulin-treated 8-weeks diabetics. EPCs were identified by flow cytometry for CD34/CD133/VEGFR2/CXCR4 antigens. Systemic SDF-1α and testosterone levels were evaluated by ELISA. Penile SDF-1α protein expression was assessed, in experimental and human diabetic cavernosal samples, by immunohistochemical techniques. Diabetic animals presented a reduction of BM-derived EPCs and an increase in putative circulating endothelial cells (CECs) sloughed from vessels wall. These alterations were rescued by insulin therapy. In addition, glycemic control promoted an increase in systemic testosterone and SDF-1α levels, which were significantly decreased in animals with diabetes. SDF-1α protein expression was reduced in experimental and human cavernosal diabetic samples, an effect prevented by insulin in treated animals. Insulin administration rescued the effects of diabetes on BM function, CECs levels, testosterone, and plasmatic/penile SDF-1α protein expression. This emphasizes the importance of glycemic control in the prevention of diabetes-induced systemic and penile EDys, by the amelioration of endothelial damage, and increase in protective pathways. J. Cell. Biochem. 118: 82-91, 2017. © 2016 Wiley Periodicals, Inc.

Saxagliptin Attenuates Albuminuria by Inhibiting Podocyte Epithelial- to-Mesenchymal Transition via SDF-1α in Diabetic Nephropathy

“…In this regard, recent data have suggested that SDF-1α was upregulated by DPP-4 inhibition and has protective roles in progressive DN ( Takashima et al, 2016 ). Previous studies have reported that SDF-1α levels were significantly reduced in both STZ-induced diabetic mice ( Gallagher et al, 2007 ; Li et al, 2012 ) and diabetic patients ( Angela Castela et al, 2017 ) compared to the normal groups, while it was markedly increased in the DPP-4 inhibitor treatment group ( Fadini et al, 2010 ; Fujita et al, 2014b ; Lovshin et al, 2017 ). In parallel with SDF-1α upregulation, DPP-4 inhibitor treatment clearly attenuated the progression of albuminuria not only in animal experiments ( Nistala et al, 2014 ) but also in clinical studies ( Fujita et al, 2014b ).…”

Estradiol correlates with erectile dysfunction and its severity in type 2 diabetic patients

“…8 Furthermore, in diabetic patients, independently from age, ED is usually more severe than in non-diabetics 9 and their glycemic control is independently associated with the risk of ED. 10,11 Recent guidelines on male sexual dysfunction recommend the assessment of hormonal status in the diagnostic flow-chart of ED. The reason is that hormones impairment is strictly involved in sexual function.…”

Proteomic analysis of oxidative stress response in human umbilical vein endothelial cells (HUVECs): role of heme oxygenase 1 (HMOX1) in hypoxanthine-induced oxidative stress in HUVECs

“…The vascular endothelium, a simple squamous epithelial layer on the surface of blood vessels, plays a major role in endocrine signaling and has a wide variety of biological functions (7,8), including the process of penile erection (9). Endothelial dysfunction, caused by harmful changes due to high glucose levels and increased oxidative stress in endothelial cells, is critical for the progression of DED (10). In addition to direct damage to endothelial cells, diabetes may hinder the angiogenesis implicated in vascular repair mechanisms, further affecting vasodilation and cavernous blood perfusion, which are essential for normal erectile function.…”