Cause Of Diabetes-related Erectile Dysfunction Is Clarified By Johns Hopkins Researchers

Researchers have found that one particular simple sugar, present inincreased levels in diabetics, interferes with the chain of eventsneeded to achieve and maintain erection and can lead to permanentpenile impairment over time. The results, which have implications fornew types of erectile dysfunction treatments targeting this mechanismof erection, are described in the August 16 issue of the Proceedings ofthe National Academy of Sciences.

Previous research had shown that diabetic erectile dysfunctionwas partially due to an interruption in an enzyme that starts the chainof vascular events leading to an erection. The Hopkins team suspectedO-GlcNAc, a blood sugar present in hyperglycemic (high blood sugar)circumstances, to be that interrupting factor.

"We were interested to determine whether high glucose indiabetes mellitus modifies the endothelial nitric oxide synthase (eNOS)enzyme, which is responsible for the achievement and maintenance oferection," says Biljana Musicki, Ph.D., lead investigator of the studyand a research associate in the Brady Urological Institute.

Erectile dysfunction is a common problem for more than half ofmen with diabetes. Musicki says that an estimated "50 percent to 75percent of diabetic men have erectile dysfunction to some degree, [arate] about threefold higher than in non-diabetic men." This is not thesame type of erectile dysfunction seen in non-diabetics, and it is lesseffectively treated with conventional drugs like Viagra.

The study examined rats with type 1 diabetes mellitus as wellas the overall mechanism of erection. "Erection begins when a sexualstimulus activates the enzyme neuronal nitric oxide synthase (nNOS)that causes short-term release of nitric oxide (NO) at the nerveendings in the penis," Musicki explains.

This initial release of NO causes rapid and short-termincreases in penile blood flow and short-term relaxation of the penilesmooth muscle, initiating an erection. The resulting expansion ofpenile blood vessels and smooth-muscle relaxation allows more blood toflow into the penis. This increased blood flow (shear stress) activatesthe eNOS in penile blood vessels causing sustained NO release,continued relaxation and full erection.

O-GlcNAc hinders this normal chain of events by inhibiting theactivation of eNOS, and consequently reducing the release of NO andpreventing the smooth muscle in the penis from relaxing. Without thisrelaxation, there is no shear stress to stoke the production of more NOand therefore, no normal, sustained erection.

The team also found that in comparison with the controls, thediabetic rats' erectile response was 30 percent lower, full erectionswere 40 percent smaller and these erections took 70 percent longer toachieve.

The study emphasizes the reduced blood vessel function presentin patients with diabetes. "The mechanism we describe here stresses thecritical importance of vascular function in the erectile response. Itmay suggest new ways of treating erectile dysfunction by targetingspecifically this mechanism in penile erection," notes Musicki.

Additionally, speaking to more than just the sexual issuesrelated to erectile dysfunction, the research addresses implicationsrelated to the overall understanding of penile health. According toArthur Burnett, M.D., a professor of urology and head of the researchteam, "eNOS plays roles in both immediate erectile response and theoverall health and function of the penile tissue."

Burnett, whose lab has studied penile erection since the early1990s, continues, "the insight here is tremendous because it speaks tofundamental biological and vascular" mechanisms of diabetes. "Thispaper gets back to the physiological relevance of hyperglycemia and howit affects erection. We show here -- using erection as a model -- thevascular damage caused by diabetes and provide insights into vasculardisease beyond this dysfunction," he adds.

The article, "Inactivation of phosphorylated endothelial nitricoxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectiledysfunction," appears in the Aug. 16 issue of the Proceedings of theNational Academy of Sciences and was published online Aug. 5. MelissaF. Kramer and Robyn E. Becker, also of the Brady Urological Institute,collaborated on this study.

This research was supportedby the National Institute of Diabetes and Digestive and Kidney Diseasesand the National Kidney Foundation of Maryland Professional DevelopmentAward.