A critical appraisal of erectile function in animal models of diabetes mellitus

作者：Gur Serap; Kadowitz Philip J; Hellstrom Wayne J G^*

来源：International Journal of Andrology, 2009, 32(2): 93-114.

DOI：10.1111/j.1365-2605.2008.00928.x

• advanced glycosylated endproduct inhibitors
• androgen
• animal models
• diabetes
• erectile dysfunction
• gene transfer
• growth hormones
• nitric oxide
• PDE-5 inhibitors
• Rho-kinase

The study of erectile function in diabetic animal models has revealed physiological alterations in neural, vascular, hormonal and endothelial function. The aims of this review are to further elucidate pathophysiological changes induced by diabetes mellitus and to introduce new concepts in the study of erectile dysED) in animal models. The recognized pathophysiological mechanisms causing diabetic ED include oxidative stress and hormonal imbalance. The evolving treatments for ED include advanced glycosylated endproduct (AGE) inhibitors, phosphodiesterase type 5 inhibitors, protein kinase C (PKC) inhibitors, hormone replacement, and gene transfer techniques. Our current understanding of how these multiple pathophysiological mechanisms contribute to ED is discussed. In this review, diabetic animal model studies have documented that oxidative stress is a pre-eminent pathophysiological mechanism and several anti-oxidants, such as alpha-lipoic acid, vitamin E, sodium selenate, melatonin, and ascorbic acid, reverse both neurogenic and endothelial dysfunction in diabetic models. Further, the peroxynitrite decomposition catalyst - FeTMPyP, PKC beta selective inhibitor - LY333531, IkappaB kinase 2 inhibitor - AS602868, AGE inhibitors - aminoguanidine and ALT-711 show promise by exploring different cellular mechanisms in treating diabetic problems. A number of vectors have been used to insert genes to increase the expression of nitric oxide synthase, superoxide dismutase, maxi-K channel (hSlo), neurotrophin-3, and vasoactive intestinal polypeptide for the treatment of erectile function. Further investigation of the hormonal treatment of diabetes associated with hypogonadism may improve sildenafil responsiveness in diabetic patients. We are optimistic that novel prevention and treatment strategies for diabetic ED are on the horizon.

• 出版日期2009-4