Sildenafil drug improves insulin sensitivity in people at risk for diabetes

Sildenafil inhibits an enzyme called phosphodiesterase 5 (PDE5), resulting in relaxation of smooth muscle, vasodilation and increased blood flow. Sildenafil is used to treat erectile dysfunction and pulmonary arterial hypertension.

Animal studies suggest that sildenafil also can improve insulin sensitivity, the uptake of glucose from the bloodstream by muscle. This action can lower the level of circulating glucose, and potentially reduce the risk of diabetes.

In the current study, overweight individuals with prediabetes were randomly assigned to receive sildenafil or placebo (inactive drug) for three months. Of the 42 subjects who completed the study, those treated with sildenafil were significantly more sensitive to insulin, the researchers reported in today's Journal of Clinical Endocrinology and Metabolism.

Sildenafil drug improves insulin sensitivity in people at risk for diabetes

Sildenafil drug may effectively relieve nerve damage in men with long-term diabetes

New animal studies at Henry Ford Hospital found that sildenafil, a drug commonly used to treat erectile dysfunction, may be effective in relieving painful and potentially life-threatening nerve damage in men with long-term diabetes.   

The research targeted diabetic peripheral neuropathy, the most common complication of diabetes, affecting as many as 70 percent of patients.

The study was recently published online in PLOS ONE. Lei Wang, M.D., the Henry Ford neuroscientist who led the research, said that although numerous drugs have been shown to be effective in earlier animal experiments, most have not provided benefits in clinical trials.

"Generally, young diabetic animals with an early stage of peripheral neuropathy are used to investigate various drug treatments," Dr. Wang explains. "But patients with diabetes who are enrolled in clinical trials often are older and have advanced peripheral neuropathy.

"Failure to develop and properly evaluate treatments in the laboratory that properly reflect the target clinical population with diabetic peripheral neuropathy may contribute to the failure of clinical trials."

To mimic clinical trials in which diabetes patients have advanced peripheral neuropathy, the Henry Ford researchers chose male mice with type II diabetes that were 36 weeks old, roughly equivalent to middle age in humans.

Sildenafil drug may effectively relieve nerve damage in men with long-term diabetes

Drug trio of rapamycin, sildenafil and doxorubicin improved effectiveness of cancer treatment, protected heart

Combining cancer medication with a drug for erectile dysfunction and one for heart transplants helped kill cancer cells and protected the heart from damage. For decades, doxorubicin has been a powerful anti-cancer treatment for various human cancers, including breast, ovarian, colon and prostate. But its use has been limited due to harmful, possibly irreversible effects on the heart.

In this study, using cell and animal models, researchers found that sildenafil alone or in combination with rapamycin (an immunosuppressant used to prevent post-transplant organ rejection) significantly improved the anti-cancer effects of doxorubicin while protecting the heart. The combination of all three medications showed the most powerful effect, researchers said.

"Because sildenafil and rapamycin are clinically approved drugs that both protect heart muscle, we thought that combining these drugs with doxorubicin would be a unique strategy to eliminate the cardiac side effects of doxorubicin while further improving its cancer-killing ability," said Rakesh Kukreja, Ph.D., study co-author and professor of internal medicine and cardiology, Virginia Commonwealth University (VCU) School of Medicine in Richmond.

"The drug combination led to a dramatic protection of heart muscle from apoptosis (cellular self-destruction) and, to a lesser extent, necrosis (cell death from disease)," said David E. Durrant, study lead author and Ph.D. candidate at the VCU School of Medicine. "We think this combination therapy may have excellent potential to move forward into clinical trials and eventually improve life expectancy of cancer patients."

Drug trio improved effectiveness of cancer treatment, protected heart