'The insight here is tremendous,' says the head of the research team, 'because it speaks to fundamental biological and vascular' mechanisms of diabetes.

One particular simple sugar, present in increased levels in diabetics, interferes with the chain of events needed to achieve and maintain erection and can lead to permanent penile impairment over time, according to researchers at the Brady Urological Institute at Johns Hopkins.

In earlier studies, diabetic erectile dysfunction was attributed in part to an interruption in an enzyme that starts the chain of vascular events leading to an erection. The Hopkins team suspected O-GlcNAc, a blood sugar present in hyperglycemic (high blood sugar) circumstances, to be that interrupting factor.

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

Common Problem Among Diabetic Men

Erectile dysfunction is a common problem for more than half of men with diabetes. An estimated "50 percent to 75 percent of diabetic men have erectile dysfunction to some degree -- [a rate] about threefold higher than in non-diabetic men," says Musicki.

This is not the same type of erectile dysfunction seen in non-diabetics, and it is less effectively treated with conventional drugs like Viagra.

"Erection begins when a sexual stimulus activates the enzyme neuronal nitric oxide synthase (nNOS) that causes short-term release of nitric oxide (NO) at the nerve endings in the penis," Musicki explains.

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

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

Insights into Vascular Disease

The research team found that rats with diabetes mellitis had an erectile response 30 percent lower than non-diabetic rats. Full erections were 40 percent smaller, and they took 70 percent longer to achieve.

The study emphasizes the reduced blood vessel function present in patients with diabetes.

"The mechanism we describe here stresses the critical importance of vascular function in the erectile response. It may suggest new ways of treating erectile dysfunction by targeting specifically this mechanism in penile erection," notes Musicki.

In addition to the sexual issues related to erectile dysfunction, the research addresses implications related to the overall understanding of penile health.

"eNOS plays roles in both immediate erectile response and the overall health and function of the penile tissue," says Arthur Burnett, MD, a professor of urology and head of the research team.

"The insight here is tremendous," continues Burnett, "because it speaks to fundamental biological and vascular" mechanisms of diabetes.

"This paper gets back to the physiological relevance of hyperglycemia and how it affects erection," he adds. "We show here -- using erection as a model -- the vascular damage caused by diabetes, and provide insights into vascular disease beyond this dysfunction."

Burnett's lab has studied penile erection since the early 1990s.