New evidence of how the elevated glucose levels that occur in diabetes damage blood vessels may lead to novel strategies for blocking the destruction, Medical College of Georgia researchers say.
They found a decreased ability of blood vessels to relax resulted from increased activity of a natural mechanism for altering protein form and function, says Dr. Rita C.Tostes, physiologist in the MCG School of Medicine.
The researchers suspect increased modification of proteins by a glucose-derived molecule is a player in vascular problems associated with hypertension, stroke and obesity as well.
One aftermath of high glucose levels is low levels of the powerful vasodilator nitric oxide in blood vessels, a shortfall that increases the risk of high blood pressure and eventual narrowing of the vessels, researchers reported at the American Society of Hypertension 24th Annual Scientific Program in San Francisco during a joint session with the Council for High Blood Pressure.
"We know diabetes is a major risk factor for cardiovascular disease and we think this is one of the reasons," Dr. Tostes says.
Diabetes increases the risk of cardiovascular disease such as heart disease and stroke, even when glucose, or blood sugar, levels are under control. In fact, about 75 percent of people with diabetes die from some form of heart or blood vessel disease, according to the American Heart Association.
Most of the glucose in the body goes directly into cells where it's modified to produce the energy source ATP. However about 5 percent of all glucose is converted to another sugar moiety, O-GlcNAc, one of the sugar types that can modify proteins.
Inside the blood vessel walls of healthy mice, MCG researchers found increased activity by O-GlcNAc competes with another mechanism for modifying proteins called phosphorylation. In blood vessels, phorphorylation modifies the enzyme that produces nitric oxide, called nitric oxide synthase, so that it makes more of the blood vessel dilator. But add more O-GlcNAc to the mix and it seems to beat phosphorylation to the punch so there is the opposite result. The longer O-GlcNAc levels were high, the worse the resulting problem, says Victor Lima, a graduate student at the University of Sao Paulo working with Dr. Tostes.