title: 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.
authors.affiliation: Faculty of Medicine, Department of Biochemistry, University of Porto, Porto, Portugal.|Institute for Molecular and Cell Biology of the University of Porto (IBMC-UP), Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
authors.forename: Angela
authors.initials: A
authors.lastname: Castela
authors.affiliation: Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gomes
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Silvestre
authors.affiliation: Animal Facility, Faculty of Medicine of the University of Porto, Porto, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Guardão
authors.affiliation: Animal Facility, Faculty of Medicine of the University of Porto, Porto, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Leite
authors.affiliation: Digital University, University of Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Chilro
authors.affiliation: Faculty of Medicine, Department of Biochemistry, University of Porto, Porto, Portugal.
authors.forename: Ilda
authors.initials: I
authors.lastname: Rodrigues
authors.affiliation: Clínica Saúde Atlântica, Clínica Urológica Vendeira, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Vendeira
authors.affiliation: Centre d'Explorations et Traitements de l'Impuissance, Paris, France.
authors.forename: Ronald
authors.initials: R
authors.lastname: Virag
authors.affiliation: Faculty of Medicine, Department of Biochemistry, University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Costa
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000097:blood*; D048909:Diabetes Complications / Q000097:blood* / Q000628:therapy; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000628:therapy; D018783:Impotence, Vasculogenic / Q000097:blood* / Q000517:prevention & control; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood*
chemical_list: D054377:Chemokine CXCL12; D013739:Testosterone
keywords: DIABETES; ENDOTHELIAL PROGENITOR CELLS; ERECTILE DYSFUNCTION; INSULIN; STROMAL DERIVED FACTOR-1 ALPHA