Diabetes has many negative effects like cardiovascular problems, chronic renal failure, retinal damage (leading to blindness), nerve damage, and microvascular damage. Now, researchers have found that the disease also creates too much competition for an amino acid called L-arginine that helps blood vessels to relax.
L-arginine, is broken down by the enzyme arginase to urea, which helps the body to get rid of toxins resulting from the proteins we eat.
The study was led by Dr. Maritza Romero, postdoctoral fellow at the Medical College of Georgia, who works in the lab of Dr. R. William Caldwell, chair of the MCG Department of Pharmacology and Toxicology.
Romero said that diabetics have a lot of arginase activity, which means they use a lot more L-arginine. He added that it also means that too little L-arginine is available to help nitric oxide synthase make nitric oxide, the powerful vasodilator that helps blood vessels relax.
It was also found that the amino acid, L-citrulline, as well as statins, compounds known to lower cholesterol, prevent increase of arginase activity, restoring normal dilation abilities in animal models of type 1 diabetes. In fact, L-citrulline can be recycled into L-arginine.
The researchers now want to find out the specific factors and pathways involved in arginase activation and develop pharmaceutical agents to combat excessive arginase activity in diabetes. They also suggest clinical trials of L-citrulline as a supplemental therapy for diabetics with vascular problems.
The results could also explain why L-arginine supplement, that was marketed to treat hypertension, chest pain, heart failure and more, may not work long term.
According to the results of an earlier study by Johns Hopkins researchers, a clinical trial of patients taking an L-arginine supplement following a heart attack didn't improve in their vascular tone or their hearts' ability to pump. In turn ut resulted in the death of more patients, who were taking L-arginine than placebo and the study was then closed with the recommendation the supplement not be used by heart attack patients. However, the supplement still is widely marketed.
"The findings of increased arginase I activity in diabetes may limit other therapeutic approaches proposed for early endothelial dysfunction such as oral L-arginine supplementation. Although dietary L-arginine supplementation has been shown to exert vascular protective effects in certain clinical settings, this approach is unlikely to be effective in diabetes, if the results of this study can be confirmed by patients in vivo. In fact, the findings of Romera et al may provide a possible explanation for the unexpected neutral or even adverse effects of oral L-arginine in some clinical studies, in particular patients with coronary artery disease and infarction," said Drs. Thomas L. Luscher and Jan Steffel, of the University of Zurich Cardiovascular Research Institute, in an accompanying editorial.
Dr. Romero said that a short intravenous course of L-arginine may provide short-term improvement in blood vessel tone. However, most of L-arginine taken directly goes to the liver to be broken down instead of the bloodstream where it can promote relaxation of blood vessels.
He said that Arginase is also associated with vascular problems related to aging, hypertension, sickle cell disease, atherosclerosis and erectile dysfunction. Apart from helping the body turn toxins into urea that can be safely eliminated from the body, arginase also helps in collagen formation and cell proliferation, but too much can be bad.
The study is published in the current issue of Circulation Research.