Researchers at the Medical College of Georgia at Augusta University have identified a mechanism by which exercise improves blood vessel health in people with type 2 diabetes. Their findings were published in Circulation Research, a journal owned by the American Heart Association.
“People with type 2 diabetes commonly have unhealthy blood vessels, which is caused by endothelial dysfunction. The inner lining of the blood vessels made up of endothelial cells doesn’t work properly, raising the risk of heart disease, stroke and poor circulation,” said Masuko Ushio-Fukai, PhD, professor of medicine in the Vascular Biology Center at MCG and co-principal investigator of the study. “Therefore, we have been studying how exercise can improve endothelial dysfunction in diabetes and addressing the mechanisms of it.”
In healthy individuals, exercise increases nitric oxide production by endothelial cells to help widen blood vessels. However, for many people with type 2 diabetes, this process is disrupted due to insulin resistance and excess oxygen production leading to endothelial dysfunction.
The research team found that exercise triggers an alternative pathway for vasodilation in those with type 2 diabetes. This involves increased expression of a copper transporter protein called ATP7A, which activates an antioxidant enzyme known as superoxide dismutase 3 (SOD3). SOD3 uses excess oxygen to produce hydrogen peroxide that then activates PKG1α protein, resulting in vasodilation.
“The superoxide dismutase, which is highly expressed in the blood vessels, is one of the keys to understanding the mechanism of how exercise improves our vascular health,” said Tohru Fukai, MD, PhD, professor of pharmacology and toxicology in the VBC and co-principal investigator.
The team used transgenic mouse models with type 2 diabetes to compare sedentary mice to those trained with exercise. They focused on small mesenteric arteries important for regulating blood flow and examined changes in antioxidant enzymes and signaling proteins following exercise.
“We isolated the blood vessels, and we checked the blood vessel function using a myograph. Then we measured the blood vessel functions, and, in the diabetic condition, the blood vessel function is impaired but was still improved by exercise,” said Sudhahar Varadarajan, PhD, associate professor of pharmacology and toxicology in the Vascular Biology Center.
When researchers genetically disabled SOD3, ATP7A or PKG1α sites in mice with diabetes who exercised, they observed that these benefits disappeared—indicating these components are essential for vasodilation.
This discovery could lead to new therapies that mimic these effects for patients unable to exercise. “The ultimate goal is to develop a sort of exercise pill for patients who can’t exercise or need additional therapy. It would be helpful to develop an exercise-equivalent medicine,” Fukai said.
Discoveries at Augusta University are changing and improving lives both within Georgia and beyond. The institution emphasizes that partnership and support are crucial as it seeks to expand its impact.
