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. This article is protected by copyright. All rights reserved.
Journal of cellular biochemistry. 2016 May 30 [Epub ahead of print]
Angela Castela, Pedro Gomes, Ricardo Silvestre, Luísa Guardão, Liliana Leite, Rui Chilro, Ilda Rodrigues, Pedro Vendeira, Ronald Virag, Carla Costa
Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal., Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal., Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal and ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal., Animal Facility, Faculty of Medicine of the University of Porto, Porto, Portugal., Animal Facility, Faculty of Medicine of the University of Porto, Porto, Portugal., Faculty of Nutrition and Food Sciences, University of Porto, Digital University, University of Porto, Porto, Portugal., Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal., Clínica Saúde Atlântica, Clínica Urológica Vendeira, Porto, Portugal., Centre d'Explorations et Traitements de l'Impuissance, Paris, France., Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal.