Erectile dysfunction and diabetes mellitus: mechanistic considerations from studies in experimental models.
Diabetes is a major risk factor for erectile dysfunction. The condition degrades both neural and vascular endothelium penile control systems. Experimental and epidemiological evidence suggest that both hyperglycemia and dyslipidemia contribute to the etiology. These are the driving forces for elevated oxidative stress and the formation of advanced glycation and lipoxygenation end products, the major target being the nitric oxide systems of nerve and endothelium. This causes reversible functional loss followed by less reversible degenerative changes. These mechanisms have direct effects, such as the nitric oxide quenching, but perhaps more importantly, indirect effects on the regulation of nitric oxide synthase expression and activity, which can involve recruitment of proinflammatory cell signaling pathways. The latter include protein kinase C, mitogen-activated kinases, and the nuclear factor kappa B cascade. Diabetes also changes the trophic influences on nerve and endothelium. Together, these form potential therapeutic targets against diabetic erectile function, and indeed vascular disease in general.
Cameron
Norman E
NE
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. n.e.cameron@abdn.ac.uk
Cotter
Mary A
MA
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D048909:Diabetes Complications / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D007172:Erectile Dysfunction / Q000209:etiology*; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000209:etiology; D008297:Male; D008954:Models, Biological; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D017127:Glycation End Products, Advanced; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein